2020 Fiscal Year Final Research Report
Mechanistic basis of new generation laminin (NGL) for developing paraxial mesoderm cell lineages from hiPSCs
Project/Area Number |
19K20671
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 90110:Biomedical engineering-related
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Research Institution | Kyoto University |
Principal Investigator |
Zhao Mingming 京都大学, iPS細胞研究所, 特定研究員 (50754206)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | 次世代ラミニン / iPS細胞 / 骨格筋幹細胞 / 再生医学 |
Outline of Final Research Achievements |
hiPSCs provide an attractive cell source of cell therapies and disease modeling for muscular dystrophy. We has established the protocol of generating muscle stem cells (MuSCs) and myocytes from hiPSCs. In this project, using next generation laminin (NGL, p421), we established more efficient protocol for generating myocytes and MuSCs. We revealed that the heparan sulfate chains (HS) in p421 regulate myogenic differentiation from hiPSCs, by regulating FGFR signaling pathway before paraxial mesoderm formation in the step-wised protocol. Utilizing the exogenous bFGF and endogenous FGFs, HS in p421 stimulated the phosphorylation of ERK in the downstream of FGFR, regulating the gene expression of primitive streak and paraxial mesoderm. In his project, we elucidated the mechanism of p421 regulating myogenic differentiation from hiPSCs and established a universal myogenic differentiation protocol for skeletal muscle disease modeling and cell therapy.
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Free Research Field |
幹細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
Using Xeno-free next generation laminin, we establish a highly efficient differentiation system from hiPSCs, providing a universal differentiation protocol for disease modeling and cell therapy. We also elucidate the role of FGFs in the next generation laminin inducing paraxial mesoderm from hiPSCs.
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