2017 Fiscal Year Final Research Report
Master regulatory factors for regeneration and EMT of kidney tubular cells
| Project/Area Number |
15K09273
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Ko Minoru 慶應義塾大学, 医学部, 教授 (50631199)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ES細胞 / iPS細胞 / 腎臓尿細管 / miRNA / 転写因子 |
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| 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.
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| Free Research Field |
腎臓内科学
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