Updated on 2026/02/20

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写真a

 
Tomohiko Akiyama
 
Organization
Graduate School of Medicine Department of Medicine Molecular Biology Assistant Professor
School of Medicine Medical Course
Title
Assistant Professor
Profile

着床前初期胚および幹細胞を対象として、転写制御およびクロマチン構造の観点から細胞運命決定機構の解明に取り組んでいる。特に、転写因子、エンハンサー、エピジェネティック因子による遺伝子発現制御機構や、性差形成に関わる分子基盤の解析を中心に研究を展開してきた。近年は、分子凝集体や液-液相分離に着目し、初期発生過程における転写制御の物性基盤の解明にも取り組んでいる。ライブイメージング、ゲノム編集、微量オミクス解析などを統合したアプローチにより、発生制御機構の包括的理解を目指している。

External link

Degree

  • 博士（生命科学） ( 東京大学 )

Research Interests

  • 転写因子

  • エピジェネティクス

  • 性差形成

  • 着床前初期発生

  • 反復配列

  • 分化制御

  • エンハンサー制御

  • 幹細胞

  • 分子凝集体（LLPS）

  • ZGA

  • 全能性

  • 転写制御

  • Mediator複合体

Research Areas

  • Life Science / Genome biology

  • Life Science / Developmental biology

  • Life Science / Molecular biology

Education

  • The University of Tokyo   Graduate School of Frontier Sciences

    2005.4 - 2008.3

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  • The University of Tokyo   Graduate School of Frontier Sciences

    2003.4 - 2005.3

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  • Waseda University   School of Science and Engineering

    1999.4 - 2003.3

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Research History

  • Yokohama City University   School of Medicine Medical Course Molecular Biology

    2022.4

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  • Keio University   School of Medicine The Sakaguchi Laboratory   Lecturer

    2020.4 - 2022.3

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  • Keio University   School of Medicine   Assistant Professor

    2018.7 - 2020.3

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  • Keio University   School of Medicine

    2013.10 - 2018.6

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  • National Institute on Aging, National Institutes of Health, USA   日本学術振興会海外特別研究員

    2011.10 - 2013.9

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  • The University of Tokyo   Graduate School of Frontier Sciences

    2008.4 - 2011.9

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  • 日本学術振興会   特別研究員(DC1)

    2005.4 - 2008.3

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Professional Memberships

  • 日本エピジェネティクス研究会

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  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

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  • THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE

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Papers

  • Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency

    Tomohiko Akiyama, Toshiya Nakahara, Saeko Sato, Kei-ichiro Ishiguro, Masashi Yukawa, Miu Yamamoto, Hidehisa Takahashi, Minoru S H Ko

    bioRxiv   2025.7

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    Authorship：Lead author,　Corresponding author   Publisher：openRxiv  

    Abstract

    The Y chromosome harbors few protein-coding genes, and their roles in early human development remain largely unclear. Here, we demonstrate that UTY, a Y-linked homolog of the histone demethylase UTX, plays a critical, demethylase-independent role in maintaining pluripotency in human embryonic stem cells (hESCs). Despite its low expression and weak enzymatic activity, UTY co-occupies active cis-regulatory elements with UTX and promotes the transcription of key pluripotency genes, including NODAL and LEFTY . Integrated genomic analyses of single and double knockout hESCs reveal that UTY and UTX function redundantly to maintain chromatin accessibility and ensure proper recruitment of core transcription factors such as OCT4 and SOX2. The combined loss of UTY and UTX disrupts transcription factor localization, induces widespread gene expression changes, and leads to a collapse of the pluripotent state, without detectable changes in H3K27 methylation. Instead, these defects are associated with impaired recruitment of ATP-dependent chromatin remodelers and reduced histone acetylation, suggesting a demethylase-independent mechanism. Our findings uncover an essential role for the evolutionarily conserved UTY in safeguarding enhancer function and transcription factor occupancy, highlighting Y-linked regulatory mechanisms that are critical for maintaining human pluripotency.

    DOI： 10.1101/2025.07.03.663017

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  • Multi-omics analysis using antibody-based in situ biotinylation technique suggests the mechanism of Cajal body formation. International journal

    Keisuke Noguchi, Hidefumi Suzuki, Ryota Abe, Keiko Horiuchi, Rena Onoguchi-Mizutani, Nobuyoshi Akimitsu, Shintaro Ogawa, Tomohiko Akiyama, Yoko Ike, Yoko Ino, Yayoi Kimura, Akihide Ryo, Hiroshi Doi, Fumiaki Tanaka, Yutaka Suzuki, Atsushi Toyoda, Yuki Yamaguchi, Hidehisa Takahashi

    Cell reports   43 ( 9 )   114734 - 114734   2024.9

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    Membrane-less subcellular compartments play important roles in various cellular functions. Although techniques exist to identify components of cellular bodies, a comprehensive method for analyzing both static and dynamic states has not been established. Here, we apply an antibody-based in situ biotinylation proximity-labeling technique to identify components of static and dynamic nuclear bodies. Using this approach, we comprehensively identify DNA, RNA, and protein components of Cajal bodies (CBs) and then clarify their interactome. By inhibiting transcription, we capture dynamic changes in CBs. Our analysis reveals that nascent small nuclear RNAs (snRNAs) transcribed in CBs contribute to CB formation by assembling RNA-binding proteins, including frontotemporal dementia-related proteins, RNA-binding motif proteins, and heterogeneous nuclear ribonucleoproteins.

    DOI： 10.1016/j.celrep.2024.114734

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  • Chimera RNA transcribed from integrated HPV18 genome with adjacent host genomic region promotes oncogenic gene expression through condensate formation. Reviewed International journal

    Kazuki Furugori, Hidefumi Suzuki, Ryota Abe, Keiko Horiuchi, Tomohiko Akiyama, Tomonori Hirose, Atsushi Toyoda, Hidehisa Takahashi

    Genes to cells : devoted to molecular & cellular mechanisms   2024.5

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    Most cervical cancers are caused by human papillomavirus (HPV) infection. In HeLa cells, the HPV18 viral genome is integrated at chromosome 8q24.21 and activates transcription of the proto-oncogene c-Myc. However, the mechanism of how the integrated HPV genome and its transcribed RNAs exhibit transcription activation function has not been fully elucidated. In this study, we found that HPV18 transcripts contain an enhancer RNA-like function to activate proximal genes including CCAT1-5L and c-Myc. We showed that the human genome-integrated HPV18 genes are activated by transcription coregulators including BRD4 and Mediator. The transcribed HPV18 RNAs form a liquid-like condensate at chromosome 8q24.21 locus, which in turn accumulates RNA polymerase II. Moreover, we focused on a relatively uncharacterized transcript from the upstream region of CCAT1, named URC. The URC RNA is transcribed as a chimera RNA with HPV18 and is composed of the 3'-untranslated region of the HPV18 transcript. We experimentally showed that the URC contributes to stabilization of HPV18 RNAs by supplying a polyadenylation site for the HPV18 transcript. Our findings suggest that integrated HPV18 at 8q24.21 locus produces HPV18-URC chimera RNA and promotes tumorigenesis through RNA-based condensate formation.

    DOI： 10.1111/gtc.13121

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  • ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes Reviewed

    Tomohiko Akiyama, Kei-ichiro Ishiguro, Nana Chikazawa, Shigeru B H Ko, Masashi Yukawa, Minoru S H Ko

    DNA Research   2023.12

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    Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    Abstract

    The Zinc finger and SCAN domain containing 4 (ZSCAN4) protein, expressed transiently in pluripotent stem cells, gametes, and early embryos, extends telomeres, enhances genome stability, and improves karyotypes in mouse embryonic stem (mES) cells. To gain insights into the mechanism of ZSCAN4 function, we identified genome-wide binding sites of endogenous ZSCAN4 protein using ChIP-seq technology in mouse and human ES cells, where the expression of endogenous ZSCAN4 was induced by treating cells with retinoic acids or by overexpressing DUX4. We revealed that both mouse and human ZSCAN4 bind to the TGCACAC motif located in CA/TG microsatellite repeats, which are known to form unstable left-handed duplexes called Z-DNA that can induce double-strand DNA breaks and mutations. These ZSCAN4 binding sites are mostly located in intergenic and intronic regions of the genomes. By generating ZSCAN4 knockout in human ES cells, we showed that ZSCAN4 does not seem to be involved in transcriptional regulation. We also found that ectopic expression of mouse ZSCAN4 enhances the suppression of chromatin at ZSCAN4-binding sites. These results together suggest that some of the ZSCAN4 functions are mediated by binding to the error-prone regions in mouse and human genomes.

    DOI： 10.1093/dnares/dsad029

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  • Joint sequence & chromatin neural networks characterize the differential abilities of Forkhead transcription factors to engage inaccessible chromatin. International journal

    Sonny Arora, Jianyu Yang, Tomohiko Akiyama, Daniela Q James, Alexis Morrissey, Thomas R Blanda, Nitika Badjatia, William K M Lai, Minoru S H Ko, B Franklin Pugh, Shaun Mahony

    bioRxiv : the preprint server for biology   2023.10

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    The DNA-binding activities of transcription factors (TFs) are influenced by both intrinsic sequence preferences and extrinsic interactions with cell-specific chromatin landscapes and other regulatory proteins. Disentangling the roles of these binding determinants remains challenging. For example, the FoxA subfamily of Forkhead domain (Fox) TFs are known pioneer factors that can bind to relatively inaccessible sites during development. Yet FoxA TF binding also varies across cell types, pointing to a combination of intrinsic and extrinsic forces guiding their binding. While other Forkhead domain TFs are often assumed to have pioneering abilities, how sequence and chromatin features influence the binding of related Fox TFs has not been systematically characterized. Here, we present a principled approach to compare the relative contributions of intrinsic DNA sequence preference and cell-specific chromatin environments to a TF's DNA-binding activities. We apply our approach to investigate how a selection of Fox TFs (FoxA1, FoxC1, FoxG1, FoxL2, and FoxP3) vary in their binding specificity. We over-express the selected Fox TFs in mouse embryonic stem cells, which offer a platform to contrast each TF's binding activity within the same preexisting chromatin background. By applying a convolutional neural network to interpret the Fox TF binding patterns, we evaluate how sequence and preexisting chromatin features jointly contribute to induced TF binding. We demonstrate that Fox TFs bind different DNA targets, and drive differential gene expression patterns, even when induced in identical chromatin settings. Despite the association between Forkhead domains and pioneering activities, the selected Fox TFs display a wide range of affinities for preexiting chromatin states. Using sequence and chromatin feature attribution techniques to interpret the neural network predictions, we show that differential sequence preferences combined with differential abilities to engage relatively inaccessible chromatin together explain Fox TF binding patterns at individual sites and genome-wide.

    DOI： 10.1101/2023.10.06.561228

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  • Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3. Reviewed International journal

    Chie Kobori, Ryo Takagi, Ryo Yokomizo, Sakie Yoshihara, Mai Mori, Hiroto Takahashi, Palaksha Kanive Javaregowda, Tomohiko Akiyama, Minoru S H Ko, Kazuo Kishi, Akihiro Umezawa

    Stem cell research & therapy   14 ( 1 )   242 - 242   2023.9

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    BACKGROUND: Melanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytes in vitro is too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps. METHOD: We differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use. RESULT: We successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice. CONCLUSION: The robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.

    DOI： 10.1186/s13287-023-03479-1

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  • MED26-containing Mediator may orchestrate multiple transcription processes through organization of nuclear bodies. International journal

    Hidefumi Suzuki, Kazuki Furugori, Ryota Abe, Shintaro Ogawa, Sayaka Ito, Tomohiko Akiyama, Keiko Horiuchi, Hidehisa Takahashi

    BioEssays : news and reviews in molecular, cellular and developmental biology   e2200178   2023.2

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    Mediator is a coregulatory complex that plays essential roles in multiple processes of transcription regulation. One of the human Mediator subunits, MED26, has a role in recruitment of the super elongation complex (SEC) to polyadenylated genes and little elongation complex (LEC) to non-polyadenylated genes, including small nuclear RNAs (snRNAs) and replication-dependent histone (RDH) genes. MED26-containing Mediator plays a role in 3' Pol II pausing at the proximal region of transcript end sites in RDH genes through recruitment of Cajal bodies (CBs) to histone locus bodies (HLBs). This finding suggests that Mediator is involved in the association of CBs with HLBs to facilitate 3' Pol II pausing and subsequent 3'-end processing by supplying 3'-end processing factors from CBs. Thus, we argue the possibility that Mediator is involved in the organization of nuclear bodies to orchestrate multiple processes of gene transcription.

    DOI： 10.1002/bies.202200178

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  • Purification of cardiomyocytes and neurons derived from human pluripotent stem cells by inhibition of de novo fatty acid synthesis. Invited Reviewed International journal

    Sho Tanosaki, Tomohiko Akiyama, Sayaka Kanaami, Jun Fujita, Minoru S H Ko, Keiichi Fukuda, Shugo Tohyama

    STAR protocols   3 ( 2 )   101360 - 101360   2022.6

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    Here we describe a protocol to obtain highly pure cardiomyocytes and neurons from human induced pluripotent stem cells (hiPSCs) via metabolic selection processes. Compared to conventional purification protocols, this approach is easier to perform and scale up and more cost-efficient. The protocol can be applied to hiPSCs and human embryonic stem cells. For complete details on the use and execution of this protocol, please refer to Tohyama et al. (2016) and Tanosaki et al. (2020).

    DOI： 10.1016/j.xpro.2022.101360

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  • Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis. Reviewed International journal

    Yuki Horisawa-Takada, Chisato Kodera, Kazumasa Takemoto, Akihiko Sakashita, Kenichi Horisawa, Ryo Maeda, Ryuki Shimada, Shingo Usuki, Sayoko Fujimura, Naoki Tani, Kumi Matsuura, Tomohiko Akiyama, Atsushi Suzuki, Hitoshi Niwa, Makoto Tachibana, Takashi Ohba, Hidetaka Katabuchi, Satoshi H Namekawa, Kimi Araki, Kei-Ichiro Ishiguro

    Nature communications   12 ( 1 )   3184 - 3184   2021.6

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    During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.

    DOI： 10.1038/s41467-021-23378-4

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  • Synthetic mRNA-based differentiation method enables early detection of Parkinson's phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells. Reviewed International journal

    Tomohiko Akiyama, Saeko Sato, Shigeru B H Ko, Osamu Sano, Sho Sato, Masayo Saito, Hiroaki Nagai, Minoru S H Ko, Hidehisa Iwata

    Stem cells translational medicine   10 ( 4 )   572 - 581   2021.4

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    Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as a nonneuronopathic subtype, is accompanied by an increased risk of Parkinson's disease. To gain insights into the association of progressive accumulation of GlcCer and the Parkinson's disease phenotypes, we generated dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) derived from a GD1 patient and a healthy donor control, and measured GlcCer accumulation by liquid chromatography-mass spectrometry. We tested two DA neuron differentiation methods: a well-established method that mimics a step-wise developmental process from iPSCs to neural progenitor cells, and to DA neurons; and a synthetic mRNA-based method that overexpresses a transcription factor in iPSCs. GD1-specific accumulation of GlcCer was detected after 60 days of differentiation by the former method, whereas it was detected after only 10 days by the latter method. With this synthetic mRNA-based rapid differentiation method, we found that the metabolic defect in GD1 patient cells can be rescued by the overexpression of wild-type GBA1 or the treatment with an inhibitor for GlcCer synthesis. Furthermore, we detected the increased phosphorylation of α-synuclein, a biomarker for Parkinson's disease, in DA neurons derived from a GD1 patient, which was significantly decreased by the overexpression of wild-type GBA1. These results suggest that synthetic mRNA-based method accelerates the analyses of the pathological mechanisms of Parkinson's disease in GD1 patients and possibly facilitates drug discovery processes.

    DOI： 10.1002/sctm.20-0302

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  • Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells. Reviewed International journal

    Sho Tanosaki, Shugo Tohyama, Jun Fujita, Shota Someya, Takako Hishiki, Tomomi Matsuura, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Tomohiko Akiyama, Yuika Morita, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Hideaki Kanazawa, Masahiro Sugimoto, Minoru S H Ko, Makoto Suematsu, Keiichi Fukuda

    iScience   23 ( 9 )   101535 - 101535   2020.9

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    The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.

    DOI： 10.1016/j.isci.2020.101535

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  • Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors. Reviewed International journal

    Yuhki Nakatake, Shigeru B H Ko, Alexei A Sharov, Shunichi Wakabayashi, Miyako Murakami, Miki Sakota, Nana Chikazawa, Chiaki Ookura, Saeko Sato, Noriko Ito, Madoka Ishikawa-Hirayama, Siu Shan Mak, Lars Martin Jakt, Tomoo Ueno, Ken Hiratsuka, Misako Matsushita, Sravan Kumar Goparaju, Tomohiko Akiyama, Kei-Ichiro Ishiguro, Mayumi Oda, Norio Gouda, Akihiro Umezawa, Hidenori Akutsu, Kunihiro Nishimura, Ryo Matoba, Osamu Ohara, Minoru S H Ko

    Cell reports   31 ( 7 )   107655 - 107655   2020.5

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    Transcription factors (TFs) play a pivotal role in determining cell states, yet our understanding of the causative relationship between TFs and cell states is limited. Here, we systematically examine the state changes of human pluripotent embryonic stem cells (hESCs) by the large-scale manipulation of single TFs. We establish 2,135 hESC lines, representing three clones each of 714 doxycycline (Dox)-inducible genes including 481 TFs, and obtain 26,998 microscopic cell images and 2,174 transcriptome datasets-RNA sequencing (RNA-seq) or microarrays-48 h after the presence or absence of Dox. Interestingly, the expression of essentially all the genes, including genes located in heterochromatin regions, are perturbed by these TFs. TFs are also characterized by their ability to induce differentiation of hESCs into specific cell lineages. These analyses help to provide a way of classifying TFs and identifying specific sets of TFs for directing hESC differentiation into desired cell types.

    DOI： 10.1016/j.celrep.2020.107655

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  • Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression Reviewed International journal

    Nishihara Koji, Shiga Takahiro, Nakamura Eri, Akiyama Tomohiko, Sasaki Takashi, Suzuki Sadafumi, Ko Minoru S. H, Tada Norihiro, Okano Hideyuki, Akamatsu Wado

    STEM CELL REPORTS   12 ( 2 )   305 - 318   2019.2

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    DOI： 10.1016/j.stemcr.2018.12.018

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  • Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors Reviewed

    Ken Hiratsuka, Toshiaki Monkawa, Tomohiko Akiyama, Yuhki Nakatake, Mayumi Oda, Sravan Kumar Goparaju, Hiromi Kimura, Nana Chikazawa-Nohtomi, Saeko Sato, Keiichiro Ishiguro, Shintaro Yamaguchi, Sayuri Suzuki, Ryuji Morizane, Shigeru B.H. Ko, Hiroshi Itoh, Minoru, S.H. Ko

    Scientific reports   9 ( doi: 10.1038/s41598-018-37485- )   2019.1

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    The derivation of kidney tissues from human pluripotent stem cells (hPSCs) and its application for replacement therapy in end-stage renal disease have been widely discussed. Here we report that consecutive transfections of two sets of synthetic mRNAs encoding transcription factors can induce rapid and efficient differentiation of hPSCs into kidney tissues, termed induced nephron-like organoids (iNephLOs). The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2+SALL1+ nephron progenitor cells with 92% efficiency within 2 days. Subsequently, the second set - HNF1A, GATA3, GATA1 and EMX2, differentiated these cells into PAX8+LHX1+ pretubular aggregates in another 2 days. Further culture in both 2-dimensional and 3-dimensional conditions produced iNephLOs containing cells characterized as podocytes, proximal tubules, and distal tubules in an additional 10 days. Global gene expression profiles showed similarities between iNephLOs and the human adult kidney, suggesting possible uses of iNephLOs as in vitro models for kidneys.<br />

    DOI： 10.1038/s41598-018-37485-8

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  • Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing Reviewed

    Tomohiko Akiyama, Saeko Sato, Nana Chikazawa-Nohtomi, Atsumi Soma, Hiromi Kimura, Shunichi Wakabayashi, Shigeru B. H. Ko, Minoru S. H. Ko

    Scientific Reports   8 ( 1 )   2018.12

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41598-017-19114-y

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  • Establishment of a rapid and footprint-free protocol for differentiation of human embryonic stem cells into pancreatic endocrine cells with synthetic mRNAs encoding transcription factors Reviewed

    Hideomi Ida, Tomohiko Akiyama, Keiichiro Ishiguro, Sravan K. Goparaju, Yuhki Nakatake, Nana Chikazawa-Nohtomi, Saeko Sato, Hiromi Kimura, Yukihiro Yokoyama, Masato Nagino, Minoru S. H. Ko, Shigeru B. H. Ko

    Stem Cell Research & Therapy   9 ( 277 )   2018.10

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    DOI： 10.1186/s13287-018-1038-3

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  • Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos Reviewed

    Kei-ichiro Ishiguro, Yuhki Nakatake, Nana Chikazawa-Nohtomi, Hiromi Kimura, Tomohiko Akiyama, Mayumi Oda, Shigeru B. H. Ko, Minoru S. H. Ko

    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL   53 ( 2 )   179 - 190   2017.2

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    DOI： 10.1007/s11626-016-0097-y

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  • Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis Reviewed

    Kei-ichiro Ishiguro, Manuela Monti, Tomohiko Akiyama, Hiromi Kimura, Nana Chikazawa-Nohtomi, Miki Sakota, Saeko Sato, Carlo Alberto Redi, Shigeru B. H. Ko, Minoru S. H. Ko

    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL   53 ( 2 )   167 - 178   2017.2

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    DOI： 10.1007/s11626-016-0096-z

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  • Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors Reviewed

    Sravan Kumar Goparaju, Kazuhisa Kohda, Keiji Ibata, Atsumi Soma, Yukhi Nakatake, Tomohiko Akiyama, Shunichi Wakabayashi, Misako Matsushita, Miki Sakota, Hiromi Kimura, Michisuke Yuzaki, Shigeru B. H. Ko, Minoru S. H. Ko

    SCIENTIFIC REPORTS   7   2017.2

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    DOI： 10.1038/srep42367

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  • Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells Reviewed International journal

    Hirayama Masatoshi, Ko Shigeru B. H, Kawakita Tetsuya, Akiyama Tomohiko, Goparaju Sravan K, Soma Atsumi, Nakatake Yuhki, Sakota Miki, Chikazawa-Nohtomi Nana, Shimmura Shigeto, Tsubota Kazuo, Ko Minoru S. H

    NPJ AGING AND MECHANISMS OF DISEASE   3   1 - 1   2017.1

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    DOI： 10.1038/s41514-016-0001-8

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  • Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells Reviewed

    Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B. H. Ko, Minoru S. H. Ko

    STEM CELLS INTERNATIONAL   2017

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    Authorship：Lead author,　Corresponding author   Language：English  

    DOI： 10.1155/2017/7215010

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  • Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cellsle Reviewed

    Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B. H. Ko, Minoru S. H. Ko

    DEVELOPMENT   143 ( 20 )   3674 - 3685   2016.10

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1242/dev.139360

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  • Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells Reviewed

    Tomohiko Akiyama, Li Xin, Mayumi Oda, Alexei A. Sharov, Misa Amano, Yulan Piao, J. Scotty Cadet, Dawood B. Dudekula, Yong Qian, Weidong Wang, Shigeru B. H. Ko, Minoru S. H. Ko

    DNA RESEARCH   22 ( 5 )   307 - 318   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1093/dnares/dsv013

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  • Maternal TET3 is dispensable for embryonic development but is required for neonatal growth Reviewed

    Yu-ichi Tsukada, Tomohiko Akiyama, Keiichi I. Nakayama

    SCIENTIFIC REPORTS   5   2015.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep15876

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  • Genome-Wide Analysis of the Chromatin Composition of Histone H2A and H3 Variants in Mouse Embryonic Stem Cells Reviewed

    Masashi Yukawa, Tomohiko Akiyama, Vedran Franke, Nathan Mise, Takayuki Isagawa, Yutaka Suzuki, Masataka G. Suzuki, Kristian Vlahovicek, Kuniya Abe, Hiroyuki Aburatani, Fugaku Aoki

    PLOS ONE   9 ( 3 )   2014.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.pone.0092689

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  • Zscan4 restores the developmental potency of embryonic stem cells Reviewed

    Tomokazu Amano, Tetsuya Hirata, Geppino Falco, Manuela Monti, Lioudmila V. Sharova, Misa Amano, Sarah Sheer, Hien G. Hoang, Yulan Piao, Carole A. Stagg, Kohei Yamamizu, Tomohiko Akiyama, Minoru S. H. Ko

    NATURE COMMUNICATIONS   4   2013.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ncomms2966

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  • The Expression and Nuclear Deposition of Histone H3.1 in Murine Oocytes and Preimplantation Embryos Reviewed

    Machika Kawamura, Tomohiko Akiyama, Satoshi Tsukamoto, Masataka G. Suzuki, Fugaku Aoki

    JOURNAL OF REPRODUCTION AND DEVELOPMENT   58 ( 5 )   557 - 562   2012.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1262/jrd.2012-074

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  • Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos Reviewed

    Buhe Nashun, Tomohiko Akiyama, Masataka G. Suzuki, Fugaku Aoki

    EPIGENETICS   6 ( 12 )   1489 - 1497   2011.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.4161/epi.6.12.18206

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  • Dynamic Replacement of Histone H3 Variants Reprograms Epigenetic Marks in Early Mouse Embryos Reviewed

    Tomohiko Akiyama, Osamu Suzuki, Junichiro Matsuda, Fugaku Aoki

    PLOS GENETICS   7 ( 10 )   2011.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1371/journal.pgen.1002279

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  • Changes in the nuclear deposition of histone H2A variants during pre-implantation development in mice Reviewed

    Buhe Nashun, Masashi Yukawa, Honglin Liu, Tomohiko Akiyama, Fugaku Aoki

    DEVELOPMENT   137 ( 22 )   3785 - 3794   2010.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1242/dev.051805

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  • Changes in H3K79 methylation during preimplantation development in mice Reviewed

    Masatoshi Ooga, Azusa Inoue, Shun-ichiro Kageyama, Tomohiko Akiyama, Masao Nagata, Fugaku Aoki

    BIOLOGY OF REPRODUCTION   78 ( 3 )   413 - 424   2008.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1095/biolreprod.107.063453

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  • Dynamics of histone H3 variant deposition during oogenesis and preimplantation development Reviewed

    Tomohiko Akiyama, Masao Nagata, Fugaku Aoki

    BIOLOGY OF REPRODUCTION   306 - 307   2008

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  • [Involvement of histone modification and histone variants replacement in genome reprogramming during oogenesis and preimplantation development].

    Fugaku Aoki, Tomohiko Akiyama

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   52 ( 16 Suppl )   2170 - 6   2007.12

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    PubMed

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  • Changes in histone modification upon activation of dormant mouse blastocysts Reviewed

    Tamako Matsuhashi, Tomohiko Akiyama, Fugaku Aoki, Senkiti Sakai

    ANIMAL SCIENCE JOURNAL   78 ( 6 )   575 - 586   2007.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/j.1740-0929.2007.00478.x

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  • The perivitelline space-forming capacity of mouse oocytes is associated with meiotic competence Reviewed

    Azusa Inoue, Tomohiko Akiyama, Masao Nagata, Fugaku Aoki

    JOURNAL OF REPRODUCTION AND DEVELOPMENT   53 ( 5 )   1043 - 1052   2007.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1262/jrd.19064

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  • Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice Reviewed

    T Akiyama, M Nagata, F Aoki

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   103 ( 19 )   7339 - 7344   2006.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.0510946103

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  • Regulation of histone acetylation during meiotic maturation in mouse oocytes Reviewed

    T Akiyama, JM Kim, M Nagata, F Aoki

    MOLECULAR REPRODUCTION AND DEVELOPMENT   69 ( 2 )   222 - 227   2004.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/mrd.20121

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MISC

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Presentations

  • Transcriptome Manipulation to Facilitate the Differentiation of Human Pluripotent Stem Cells

    秋山智彦

    幹細胞シンポジウム（招待講演）  2018.6 

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  • ヒトES細胞の直接分化誘導に関わるaccessible chromatin構造

    秋山智彦

    次世代生命科学研究会（招待講演）  2017.7 

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  • Accelerated differentiation of human pluripotent stem cells by ectopic expression of histone demethylase

    秋山智彦

    日本発生生物学会（招待講演）  2017.5 

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  • 転写因子導入によるヒト多能性幹細胞の分化誘導の自在化を目指して

    秋山智彦

    熊本大学発生研セミナー（招待講演）  2017.12 

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  • 転写因子およびクロマチン制御因子による分化誘導の自在化を目指して

    秋山智彦

    分子生物学会フォーラム（招待講演）  2017.12 

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  • 合成 RNA による骨格筋分化誘導法の確立

    秋山智彦

    骨格筋領域カンファレンス（招待講演）  2017.2 

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  • マウスES細胞のゲノム安定性に寄与するクロマチンリセット機構

    秋山智彦

    理化学研究所バイオリソースセンター（招待講演）  2016.1 

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  • Corporative roles of UTX and UTY in human embryonic stem cells Invited

    新学術領域「非ゲノム情報複製」国際Webinar  2021.6 

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  • ２つのヒストン脱メチル化酵素により制御される転写調節機構 Invited

    熊本大学発生研教育セミナー  2019.1 

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  • 多能性幹細胞における転写因子配置調節機構 Invited

    日本遺伝学会・新学術領域「非ゲノム情報複製」共催シンポジウム  2021.9 

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  • Y染色体上遺伝子UTYによる転写調節機構がヒト胚発生を制御する Invited

    日本分子生物学会  2023.12 

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  • Corporative roles of UTX and UTY in human embryonic stem cells Invited

    日本細胞生物学会・新学術領域「非ゲノム情報複製」共催シンポジウム  2022.6 

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  • マウス胚を用いたメディエーター複合体によるZGA転写制御機構の解明 Invited

    日本分子生物学会  2025.12 

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  • Duxによる非空間的転写調節機構の解明 Invited

    日本生化学会  2024.11 

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Awards

  • Excellent Doctoral Thesis Award

    2008.3   東京大学  

    秋山智彦

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Research Projects

  • ES細胞の分化過程において切り替わる転写調節機構の解明

    Grant number：22K06090  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    秋山 智彦

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

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  • 多能性を規定するエンハンサーループの維持と再構築機構の解明

    Grant number：22H04699  2022.4 - 2024.3

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    秋山 智彦

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    Grant amount：\8580000 （ Direct Cost: \6600000 、 Indirect Cost：\1980000 ）

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  • 武田薬品COCKPI-T® Funding

    2021 - 2022

    武田薬品株式会社共同研究費  武田薬品株式会社共同研究費

    秋山 智彦

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    Authorship：Principal investigator 

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  • 転写装置の性差形成機構の解明

    Grant number：20H04929  2020.4 - 2022.3

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    秋山 智彦

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    Grant amount：\10400000 （ Direct Cost: \8000000 、 Indirect Cost：\2400000 ）

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  • 幹細胞のエンハンサー機能を支えるクロマチン継承機構

    Grant number：20H05395  2020.4 - 2022.3

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    秋山 智彦

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    Grant amount：\8320000 （ Direct Cost: \6400000 、 Indirect Cost：\1920000 ）

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  • The roles of histone demethylases in transcriptional process involved in cell differentiation

    Grant number：19K06492  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Akiyama Tomohiko

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    In this study, we found that UTX regulates pluripotency of human ES cells by the demethylase activity independent pathway. Therefore, we focused on UTY, a homolog of UTX, which is encoded on the Y chromosome. UTY is evolutionarily mutated in the enzyme activity and has no demethylation function. When both UTX and UTY were deleted, abnormalities in gene expression were observed globally in undifferentiated ES cells and differentiated cells. Furthermore, the localization of transcription factors that bind to enhancer regions was altered in thousands of locations. These results indicate that UTX and UTY regulate transcription factor positioning in a demethylase-independent manner and are involved in the regulation of ES cell differentiation.

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  • COCKPITプラットフォーム開発

    2018 - 2019

    武田薬品株式会社共同研究費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • ヒストン脱メチル化酵素の局在を決定する因子の探索

    2018

    熊本大学発生医研究所共同研究費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • In vitroにおける神経筋接合部のモデル構築

    2018

    慶應義塾大学医学部坂口光洋記念研究奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • Elucidating of transcription factor network during the differentiation of human ES cells

    Grant number：17K15129  2017.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    AKIYAMA TOMOHIKO

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    Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

    ATAC sequencing was performed to identify open chromatin that regulates differentiation of human ES cells by introduction of transcription factors. Skeletal muscle differentiation by introducing MYOD1 and neuronal differentiation by introducing NGN2 was analysed and we identified several thousands of open chromatin sites specifically present in the differentiated cells. In addition to the sites that MYOD1 and NGN2 originally bind to in adult tissues, there were open chromatin sites that appear specifically when MYOD1 and NGN2 were introduced into ES cells. Together, direct conversions of ES cells to terminally differentiated cells can be achieved by the coordinated action controlled by these two types of open chromatin sites.

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  • 組織幹細胞の維持・若返りを可能にする新規分子メカニズム

    2017 - 2020

    科学研究費補助金・基盤研究（A） 

    洪実

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    Grant type：Competitive

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  • ヒトES細胞の分化過程における転写因子ネットワークの解明と新規分化誘導因子の同定

    2017 - 2018

    科学研究費補助金・若手研究（Ｂ） 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • 分化制御に関わるヒストン脱メチル化酵素複合体の構造と機能解析

    2017

    熊本大学発生医研究所共同研究費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • オープンクロマチン解析法を用いたヒト胚性幹細胞の分化誘導過程における転写因子ネットワークの構造解明と新規細胞分化誘導因子同定法の開発

    2016

    慶應義塾大学医学部坂口光洋記念研究奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • ヒストン脱メチル化酵素を用いた多能性幹細胞からの分化誘導促進法の開発

    2015 - 2016

    日本医療研究開発機構橋渡し研究シーズA 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • トランスクリプトーム変換システムによる分化誘導の自在化

    2015

    慶應義塾大学医学部坂口光洋記念研究奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • エピゲノム制御によるヒト多能性幹細胞の分化操作

    2015

    慶應義塾大学医学部研究奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • ヒト多能性幹細胞から骨格筋細胞への直接分化誘導におけるゲノム高次構造の動態解析

    2014

    慶應義塾大学医学部研究奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • 体細胞クローンにおけるゲノムリプログラミングへのヒストン変異体置換の関与

    2010 - 2011

    科学研究費補助金・若手研究（Ｂ） 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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  • マウス卵子における遺伝子発現プログラムの初期化機構に関する研究

    2005 - 2007

    科学研究費補助金・特別研究員奨励費 

    秋山智彦

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    Authorship：Principal investigator  Grant type：Competitive

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Social Activities

  • 生殖細胞・生殖系列に関する生命倫理セミナー

    Role(s)： Lecturer

    慶應義塾大学生命倫理委員会  2018.3

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  • ヒトES細胞従事者に対する倫理講習会

    Role(s)： Lecturer

    理科学研究所バイオリソースセンター 2021年2月26日 

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    Type：Seminar, workshop

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