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Investigation of the molecular basis of extraembryonic lineage specification in humans

Research Project

Project/Area Number 18K09216
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionTohoku University

Principal Investigator

Hiroaki Okae  東北大学, 医学系研究科, 准教授 (10582695)

Co-Investigator(Kenkyū-buntansha) 有馬 隆博  東北大学, 医学系研究科, 教授 (80253532)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsヒト胎盤 / 胎盤トロフォブラスト幹(TS)細胞 / エピジェネティクス / ダイレクトリプログラミング / 胎盤トロフォブラスト幹(TS)細胞
Outline of Final Research Achievements

A mammalian zygote undergoes cleavage divisions to form a blastocyst that is composed of inner cell mass (ICM) and trophectoderm (TE). In mice, many transcription factors including CDX2 and EOMES have been identified as essential for the specification of the TE lineage. However, little is known about how the TE lineage is specified in human preimplantation embryos. This study aimed to identify factors involved in this process. To this end, we identified transcription factors specifically expressed in undifferentiated human TS cells. Although it turned out to be difficult to derive induced TS (iTS) cells from somatic cells with these transcription factors, we successfully converted human ES/iPS cells into iTS cells by overexpressing GATA2, GATA3, or TFAP2A. These transcription factors may be involved in the regulation of early lineage specification in humans.

Academic Significance and Societal Importance of the Research Achievements

ヒトiTS細胞の誘導に有効であったGATA2、GATA3、TFAP2Aは、マウスの胎盤発生においても重要な役割を担うことが報告されている。一方、CDX2やEOMESを用いてヒトiTS細胞を誘導することはできない。よって、TE系譜への運命決定機構は、ヒトとマウスの間で一部保存されていることが明らかとなった。ヒト着床前胚における細胞運命決定機構の理解は、不妊や流産の原因の解明や、安全な生殖補助医療の提供などに役立つと期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (37 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 14 results) Book (5 results)

  • [Int'l Joint Research] CBI Toulouse/Universite de Nantes(フランス)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] McGill University/University of Western Ontario(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Kansas Medical Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2019 Research-status Report
  • [Journal Article] ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development2021

    • Author(s)
      Varberg Kaela M.、Iqbal Khursheed、Muto Masanaga、Simon Mikaela E.、Scott Regan L.、Kozai Keisuke、Choudhury Ruhul H.、Aplin John D.、Biswell Rebecca、Gibson Margaret、Okae Hiroaki、Arima Takahiro、Vivian Jay L.、Grundberg Elin、Soares Michael J.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 10

    • DOI

      10.1073/pnas.2016517118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome2020

    • Author(s)
      Cinkornpumin Jessica K.、Kwon Sin Young、Guo Yixin、Hossain Ishtiaque、Sirois Jacinthe、Russett Colleen S.、Tseng Hsin-Wei、Okae Hiroaki、Arima Takahiro、Duchaine Thomas F.、Liu Wanlu、Pastor William A.
    • Journal Title

      Stem Cell Reports

      Volume: 15 Issue: 1 Pages: 198-213

    • DOI

      10.1016/j.stemcr.2020.06.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts2020

    • Author(s)
      Jaju Bhattad Gargi、Jeyarajah Mariyan J.、McGill Megan G.、Dumeaux Vanessa、Okae Hiroaki、Arima Takahiro、Lajoie Patrick、B?rub? Nathalie G.、Renaud Stephen J.
    • Journal Title

      Cell Death & Disease

      Volume: 11 Issue: 5 Pages: 311-327

    • DOI

      10.1038/s41419-020-2500-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Atypical protein kinase C iota (PKCλ/ι) ensures mammalian development by establishing the maternal?fetal exchange interface2020

    • Author(s)
      Bhattacharya Bhaswati、Home Pratik、Ganguly Avishek、Ray Soma、Ghosh Ananya、Islam Md. Rashedul、French Valerie、Marsh Courtney、Gunewardena Sumedha、Okae Hiroaki、Arima Takahiro、Paul Soumen
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 25 Pages: 14280-14291

    • DOI

      10.1073/pnas.1920201117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Unique features and emerging in vitro models of human placental development.2020

    • Author(s)
      Shun Shibata, Eri H Kobayashi, Norio Kobayashi, Akira Oike, Hiroaki Okae, Takahiro Arima.
    • Journal Title

      Reprod Med Biol .

      Volume: 12 Issue: 4 Pages: 301-313

    • DOI

      10.1002/rmb2.12347

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells2020

    • Author(s)
      Castel G, Meistermann D, Bretin B, Firmin J, Blin J, Loubersac S, Bruneau A, Chevolleau S, Kilens S, Chariau C, Gaignerie A, Francheteau Q, Kagawa H, Charpentier E, Flippe L, Francois-Campion V, Haider S, Dietrich B, Knofler M, Arima T, Bourdon J, Rivron N, Masson D, Fournier T, Okae H, Freour T, David L
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 8 Pages: 108419-108419

    • DOI

      10.1016/j.celrep.2020.108419

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] G protein subunit β1 is an important mediator of the late stage of endochondral ossification2020

    • Author(s)
      Ruengsinpinya Lerdluck、Murakami Tomohiko、Nakamura Eriko、Takahata Yoshifumi、Hata Kenji、Nakaminami Yuri、Okae Hiroaki、Nishimura Riko
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 533 Issue: 1 Pages: 90-96

    • DOI

      10.1016/j.bbrc.2020.08.119

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of four imprinting disorders and ART2019

    • Author(s)
      Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
    • Journal Title

      Clin Epigenetics

      Volume: 11 Issue: 1 Pages: 21-21

    • DOI

      10.1186/s13148-019-0623-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of p57KIP2expression confers resistance to contact inhibition in human androgenetic trophoblast stem cells2019

    • Author(s)
      Takahashi Sota、Okae Hiroaki、Kobayashi Norio、Kitamura Akane、Kumada Kanako、Yaegashi Nobuo、Arima Takahiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 52 Pages: 26606-26613

    • DOI

      10.1073/pnas.1916019116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cutting Edge: G Protein Subunit b 1 Negatively Regulates NLRP3 Inflammasome Activation2019

    • Author(s)
      Tomohiko Murakami, Lerdluck Ruengsinpinya, Eriko Nakamura,Yoshifumi Takahata, Kenji Hata, Hiroaki Okae,Shun’ichiro Taniguchi, Masafumi Takahashi and Riko Nishimura
    • Journal Title

      The Journal of Immunology

      Volume: 202 Issue: 7 Pages: 1942-1947

    • DOI

      10.4049/jimmunol.1801388

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of four imprinting disorders and ART.2019

    • Author(s)
      Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Pages: 21-21

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactate dehydrogenase C is required for the protein expression of a sperm-specific isoform of lactate dehydrogenase A2018

    • Author(s)
      Dodo Mina、Kitamura Hiroshi、Shima Hiroki、Saigusa Daisuke、Wati Sisca Meida、Ota Nao、Katsuoka Fumiki、Chiba Hatsune、Okae Hiroaki、Arima Takahiro、Igarashi Kazuhiko、Koseki Takeyoshi、Sekine Hiroki、Motohashi Hozumi
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 4 Pages: 323

    • DOI

      10.1093/jb/mvy108

    • NAID

      40021893390

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivation of Human Trophoblast Stem Cells.2018

    • Author(s)
      Okae H, Toh H, Sato T, Hiura H, Takahashi S, Shirane K, Kabayama Y, Suyama M, Sasaki H, Arima T.
    • Journal Title

      Cell Stem Cell

      Volume: 22 Pages: 50-63

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトES細胞からTS細胞への分化転換を阻害するエピジェネティックバリアの同定2021

    • Author(s)
      岡江寛明
    • Organizer
      AMED研究開発交流会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Modeling human placental development and disease with stem cells2021

    • Author(s)
      岡江寛明
    • Organizer
      第9回 東北大学スマート・エイジング学際重点研究センター シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 分化全能性の消失に関わるインプリント遺伝子の同定2020

    • Author(s)
      岡江寛明、小林記緒、有馬隆博
    • Organizer
      日本繁殖生物学会第113回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Epigenetic restriction of human pluripotency by silencing of the chromosome 19 miRNA cluster2020

    • Author(s)
      岡江寛明
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 着床前胚に由来する幹細胞を用いた全能性の再構築2020

    • Author(s)
      岡江寛明
    • Organizer
      新学術領域研究「全能性プログラム」Webinar
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Identification of an epigenetic barrier between human embryonic and trophoblast stem cells2020

    • Author(s)
      岡江寛明
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ヒトES細胞からTS細胞への運命転換2020

    • Author(s)
      岡江寛明
    • Organizer
      新学術領域研究「配偶子インテグリティの構築」「全能性プログラム」合同公開シンポジウム2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] なぜ絨毛癌は稀なのか?ヒト栄養膜幹細胞を用いた胎盤の腫瘍化抑制機構の解析2019

    • Author(s)
      岡江 寛明
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト胚性幹細胞の栄養膜幹細胞への分化転換2019

    • Author(s)
      小林 記緒
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒト胎盤異常のエピゲノム~全胞状奇胎の細胞特性の解析~2019

    • Author(s)
      有馬 隆博
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト胎盤幹(TS)細胞の樹立とその細胞特性2019

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第14回日本生殖発生医学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Derivation of Human Trophoblast Stem Cells from Blastocysts and Villous Cytotrophoblast Cells.2019

    • Author(s)
      Okae H. ArimaT.
    • Organizer
      International Symposium on Epigenome 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト胎盤のトロフォブラスト幹細胞の樹立と臨床への応用2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] ARTによるエピジェネティクスの変調2018

    • Author(s)
      小林記緒、樋浦仁、岡江寛明、有馬隆博
    • Organizer
      第63回日本生殖医学会学術講演会・総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Derivation of human trophoblast stem cells.2018

    • Author(s)
      Okae H. ArimaT.
    • Organizer
      Cold Spring Harbor Asia meeting on Stem Cell Crossroads.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 加齢によるエピジェネティクス変異2019

    • Author(s)
      服部裕充、小林記緒、岡江寛明、有馬隆博
    • Total Pages
      7
    • Publisher
      医学書院
    • Related Report
      2019 Research-status Report
  • [Book] プラダー・ウィリ症候群2019

    • Author(s)
      岡江寛明, 有馬隆博.
    • Total Pages
      1
    • Publisher
      雑誌診断と治療社
    • Related Report
      2019 Research-status Report
  • [Book] プラダー・ウィリ症候群.2019

    • Author(s)
      岡江寛明, 有馬隆博.
    • Total Pages
      1
    • Publisher
      雑誌診断と治療社
    • Related Report
      2018 Research-status Report
  • [Book] ヒト栄養膜幹細胞の樹立.2018

    • Author(s)
      岡江寛明, 有馬隆博.
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2018 Research-status Report
  • [Book] Therapeutic approaches to imprinting diseases. Epigenetics in Human Disease,2018

    • Author(s)
      Hattori H, Hiura H, Kobayashi N, Takahashi S, Okae H, Arima T.
    • Total Pages
      6
    • Publisher
      Academic Press.
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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