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Renal tubular cells derived from human ES cells and hepatocytes by transcription factor administration

Research Project

Project/Area Number 16H07177
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionKeio University

Principal Investigator

Hiratsuka Ken  慶應義塾大学, 医学部(信濃町), 助教 (80594481)

Research Collaborator KO Minoru  慶應義塾大学, 医学部, 教授 (50631199)
Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsヒトES細胞 / 転写調節因子 / リプログラミング / 腎臓再生 / 多能制幹細胞 / 転写因子 / 再生医療 / 腎尿細管細胞 / ヒト多能性幹細胞 / 肝細胞 / 尿細管細胞
Outline of Final Research Achievements

We utilized the transcription factor (TF)-inducible human ES lines, analyzed correlation of gene expression response to the induction of human TFs with tissue-specific gene expression in silico, and identified candidate TFs for differentiating towards renal lineages. Based on in-silico analysis, we have identified a set of four TFs that induce nephron progenitor cells (NPCs) and another set of four TFs that help differentiate toward pretubular aggregate-like cells. Two days after the transfection of the first set of four TFs together into hESCs, NPCs were induced efficiently (~92%). Subsequent administration of the second set of four TFs transfection induced differentiation into pretubular aggregate-like cells. On day 14, epithelial characteristic changes and multi-segmented kidney structures containing podocyte, proximal tubules, and distal tubules were observed in 3D cultures. RNA-Seq analysis also showed the global expression profile closely resembled human kidney profile.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • Research Products

    (3 results)

All 2017 2016

All Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Multi-segmented kidney organoids derived from human ES cells by stepwise transcription factor administration2017

    • Author(s)
      Ken Hiratsuka, Toshiaki Monkawa, Shintaro Yamaguchi, Ryuji Morizane, Shigeru B.H. Ko, Hiroshi Itoh, Minoru S.H. Ko
    • Organizer
      Kidney Week(ASN)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel method to differentiate human ES cells into renal tubule-like cells by a combination of transcription factors administration2016

    • Author(s)
      Ken Hiratsuka, Toshiaki Monkawa, Shintaro Yamaguchi, Ryuji Morizane, Shigeru B.H. Ko, Hiroshi Itoh, Minoru S.H. Ko
    • Organizer
      Kidney Week2016(ASN)
    • Place of Presentation
      Chicago, IL
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト尿細管マスター制御因子の検索と、転写因子をコードする修飾合成mRNAを用いたヒト多能性幹細胞から尿細管様細胞への分化誘導方法の開発2016

    • Author(s)
      平塚 健, 門川俊明, 秋山智彦, 中武悠樹, Sravan Kumar Goparaju, 小林紗恵子, 納富奈々, 木村寛美, 山口慎太郎, 森實隆司, 鈴木さゆり, 洪 繁, 洪 実, 伊藤 裕
    • Organizer
      第7回分子腎臓フォーラム
    • Place of Presentation
      ベルサール八重洲
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report

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Published: 2016-09-02   Modified: 2019-03-29  

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