Akiyama, Tomohiko

写真a

Affiliation

School of Medicine, The Sakaguchi Laboratory - Department of Systems Medicine (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Career 【 Display / hide

  • 2008.04
    -
    2011.06

    The University of Tokyo, Graduate School of Frontier Sciences, 特任研究員

  • 2011.10
    -
    2013.09

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

  • 2013.10
    -
    2018.06

    Keio University, 医学部坂口記念システム医学講座, 特任助教

  • 2018.07
    -
    Present

    慶應義塾大学, 医学部坂口記念システム医学講座, 助教

Academic Background 【 Display / hide

  • 2005.04
    -
    2008.03

    The University of Tokyo, Graduate School of Frontier Sciences

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(生命科学), 東京大学大学院, Coursework, 2008.03

 

Research Areas 【 Display / hide

  • Genome biology

  • Molecular biology

  • Developmental biology

 

Books 【 Display / hide

  • Zscan4による特異的なヘテロクロマチン制御を介したマウスES細胞のゲノム安定化

    Akiyama Tomohiko, 細胞工学, 2015.11

  • 転写因子操作による多能性幹細胞からの自在な細胞分化誘導技術の確立を目指して

    Akiyama Tomohiko, 日本臨牀, 2015.06

  • 着床前期胚、生殖細胞、多能性幹細胞、組織性幹細胞に関わるZSCAN4

    Akiyama Tomohiko, 実験医学, 2014.04

  • 卵形成・初期発生過程におけるゲノム再プログラム化とヒストン修飾・ヒストン変異体置換

    AKIYAMA Tomohiko, 蛋白質核酸酵素, 2007.12

  • 減数分裂期の染色体分配とクロマチン修飾

    AKIYAMA Tomohiko, 細胞工学, 2006.09

Papers 【 Display / hide

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

    Hiratsuka K., Monkawa T., Akiyama T., Nakatake Y., Oda M., Goparaju S., Kimura H., Chikazawa-Nohtomi N., Sato S., Ishiguro K., Yamaguchi S., Suzuki S., Morizane R., Ko S., Itoh H., Ko M.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019.12

     View Summary

    © 2019, The Author(s). 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.

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

    Nishihara K., Shiga T., Nakamura E., Akiyama T., Sasaki T., Suzuki S., Ko M., Tada N., Okano H., Akamatsu W.

    Stem Cell Reports (Stem Cell Reports)  12 ( 2 ) 305 - 318 2019.02

    ISSN  22136711

     View Summary

    © 2019 The Authors Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3β (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state.

  • 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 10 Technology 1004 Medical Biotechnology

    Ida H., Akiyama T., Ishiguro K., Goparaju S., Nakatake Y., Chikazawa-Nohtomi N., Sato S., Kimura H., Yokoyama Y., Nagino M., Ko M., Ko S.

    Stem Cell Research and Therapy (Stem Cell Research and Therapy)  9 ( 1 )  2018.10

     View Summary

    © 2018 The Author(s). Background: Transplantation of pancreatic β cells generated in vitro from pluripotent stem cells (hPSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) has been proposed as an alternative therapy for diabetes. Though many differentiation protocols have been developed for this purpose, lentivirus-mediated forced expression of transcription factors (TF) - PDX1 and NKX6.1 - has been at the forefront for its relatively fast and straightforward approach. However, considering that such cells will be used for therapeutic purposes in the future, it is desirable to develop a procedure that does not leave any footprint on the genome, as any changes of DNAs could potentially be a source of unintended, concerning effects such as tumorigenicity. In this study, we attempted to establish a novel protocol for rapid and footprint-free hESC differentiation into a pancreatic endocrine lineage by using synthetic mRNAs (synRNAs) encoding PDX1 and NKX6.1. We also tested whether siPOU5F1, which reduces the expression of pluripotency gene POU5F1 (also known as OCT4), can enhance differentiation as reported previously for mesoderm and endoderm lineages. Methods: synRNA-PDX1 and synRNA-NKX6.1 were synthesized in vitro and were transfected five times to hESCs with a lipofection reagent in a modified differentiation culture condition. siPOU5F1 was included only in the first transfection. Subsequently, cells were seeded onto a low attachment plate and aggregated by an orbital shaker. At day 13, the degree of differentiation was assessed by quantitative RT-PCR (qRT-PCR) and immunohistochemistry for endocrine hormones such as insulin, glucagon, and somatostatin. Results: Both PDX1 and NKX6.1 expression were detected in cells co-transfected with synRNA-PDX1 and synRNA-NKX6.1 at day 3. Expression levels of insulin in the transfected cells at day 13 were 450 times and 14 times higher by qRT-PCR compared to the levels at day 0 and in cells cultured without synRNA transfection, respectively. Immunohistochemically, pancreatic endocrine hormones were not detected in cells cultured without synRNA transfection but were highly expressed in cells transfected with synRNA-PDX1, synRNA-NKX6.1, and siPOU5F1 at as early as day 13. Conclusions: In this study, we report a novel protocol for rapid and footprint-free differentiation of hESCs to endocrine cells.

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

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

    SCIENTIFIC REPORTS (Scientific Reports)  8 ( 1 ) 1043 - 1052 2018.01

    Research paper (scientific journal),  ISSN  2045-2322

     View Summary

    © 2018 The Author(s). Direct generation of skeletal muscle cells from human pluripotent stem cells (hPSCs) would be beneficial for drug testing, drug discovery, and disease modelling in vitro. Here we show a rapid and robust method to induce myogenic differentiation of hPSCs by introducing mRNA encoding MYOD1 together with siRNA-mediated knockdown of POU5F1 (also known as OCT4 or OCT3/4). This integration-free approach generates functional skeletal myotubes with sarcomere-like structure and a fusion capacity in several days. The POU5F1 silencing facilitates MYOD1 recruitment to the target promoters, which results in the significant activation of myogenic genes in hPSCs. Furthermore, deep sequencing transcriptome analyses demonstrated that POU5F1-knockdown upregulates the genes associated with IGF- and FGF-signaling and extracellular matrix that may also support myogenic differentiation. This rapid and direct differentiation method may have potential applications in regenerative medicine and disease therapeutics for muscle disorders such as muscular dystrophy.

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

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

    STEM CELLS INTERNATIONAL    1043 - 1052 2017.04

    Research paper (scientific journal),  ISSN  1687-966X

display all >>

Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 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

    2020.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 秋山 智彦, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 転写装置の性差形成機構の解明

    2020.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 秋山 智彦, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 分化制御を担う転写プロセスにおけるヒストン脱メチル化酵素の役割

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 秋山 智彦, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 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

    2017.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 秋山 智彦, Grant-in-Aid for Young Scientists (B), Principal Investigator