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Master regulatory factors for regeneration and EMT of kidney tubular cells

Research Project

Project/Area Number 15K09273
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKeio University

Principal Investigator

Monkawa Toshiaki  慶應義塾大学, 医学部(信濃町), 教授 (80286484)

Co-Investigator(Renkei-kenkyūsha) Ko Minoru  慶應義塾大学, 医学部, 教授 (50631199)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsES細胞 / iPS細胞 / 腎臓尿細管 / miRNA / 転写因子 / micro RNA / 腎線維化 / 尿細管 / 再生 / 腎臓 / 尿細管細胞 / EMT
Outline of Final Research Achievements

Based on in-silico analysis, we have identified the first set of four transcription factors to enhance the differentiation from hPSCs into SIX2+SALL1+ nephron progenitor cells (NPCs) with 92% efficiency within 2 days of reprogramming. The second set of four transcription factors converted SIX2+ NPCs into kidney organoids which contain multi-segmented nephron structures with characteristics of podocytes, proximal and distal tubules on day 14. This novel method using synthetic mRNAs might provide safe cellular sources without genome modifications for kidney regenerative therapies as wells as for disease modeling and drug screening in vitro.
Overexpression of miR-363 induced mesenchymal phenotypes with loss of epithelial phenotypes in human kidney tubular HKC-8 cells. We identified TWIST/canonical WNT pathway as the downstream effecter of miR-363, and inhibition of canonical WNT by small molecule, IWR-1, attenuated EMT induced by miR-363.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype2016

    • Author(s)
      Morizane R, Fujii S, Monkawa T, Hiratsuka K, Yamaguchi S, Homma K, Itoh H.
    • Journal Title

      Clin Exp Nephrol

      Volume: 20 Issue: 3 Pages: 394-401

    • DOI

      10.1007/s10157-015-1167-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 2017(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
      シカゴ(米国)
    • Year and Date
      2016-11-15
    • Related Report
      2016 Research-status 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(東京都中央区)
    • Related Report
      2016 Research-status Report
  • [Presentation] The Direct Differentiation Method of Renal Tubular Cells by Synthetic mRNAs of Transcription Factors Identi ed from TF-Inducible Human ES Bank2015

    • Author(s)
      Ken Hiratsuka, Toshiaki Monkawa, Shintaro Yamaguchi, Ryuji Morizane, Shigeru B.h. Ko, Minoru S.h. Ko, Hiroshi Itoh
    • Organizer
      Kidney Week 2015
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2015-11-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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