Mechanistic basis of new generation laminin (NGL) for developing paraxial mesoderm cell lineages from hiPSCs
Project/Area Number |
19K20671
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 90110:Biomedical engineering-related
|
Research Institution | Kyoto University |
Principal Investigator |
Zhao Mingming 京都大学, iPS細胞研究所, 特定研究員 (50754206)
|
Project Period (FY) |
2019-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 次世代ラミニン / iPS細胞 / 骨格筋幹細胞 / 再生医学 |
Outline of Research at the Start |
Our previous work shows coating culture dish with new generation laminin (NGL) improved hiPSCs differentiation. Here, we seek to elucidate the deeper mechanism of NGL regulating hiPSCs differentiation, contributing to a better understanding of the role of NGL in hiPSCs differentiation.
|
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.
|
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.
|
Report
(3 results)
Research Products
(7 results)
-
-
[Journal Article] Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model2020
Author(s)
Mingming Zhao, Atsutoshi Tazumi, Satoru Takayama, Nana Takenaka-Ninagawa, Minas Nalbandian, Miki Nagai, Yumi Nakamura, Masanori Nakasa, Akira Watanabe, Makoto Ikeya, Akitsu Hotta, Yuta Ito, Takahiko Sato, and Hidetoshi Sakurai
-
Journal Title
Stem Cell Reports
Volume: 15
Issue: 1
Pages: 80-94
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
-
-
-