Recapitulating Human Brown Adipose Tissue from Pluripotent Stem Cells
Project/Area Number |
21K08528
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-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)
|
Project Period (FY) |
2021-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | Brown adipose tissue / iPSC / Stem cells / brown adipose tissue / obesity / regenerative medicine |
Outline of Research at the Start |
Increasing human brown adipose tissue (hBAT) mass and activity in humans offers a unique opportunity to treat obesity and metabolic syndrome. In this project, we will establish a protocol to differentiate hiPSCs into BAT by following embryonic development. RNA-seq will be used to identify key regulators of hBAT development and the surface markers for the purification of BAT progenitors. BAT-specific transcriptome markers and thermogenic function will be analyzed in hiPSC-BAT in vitro. The anti-obesity effects will be evaluated by transplanting hiPSC-BAT into immunodeficient obesity rats.
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Outline of Annual Research Achievements |
We have established a highly efficient protocol to differentiate hiPSCs to Paraxial mesoderm and Dermomyotome. We also have established an hiPSC MYF5-tdTomato reporter cell line by the Cas9/CRISPR system. Using this cell line, we could achieve MYF5+ BAT progenitor cells and purify the MYF5+ cells by FACS, and then stimulate the brown adipocyte differentiation in SFO3 supplemented with adipose differentiation cocktails. After 80 days of differentiation, cells stored small multilocular lipid droplets. RNA-seq data indicated that the brown adipocyte marker genes PPARα, PGC1α, CEBPα, CEBPβ, PPARγ were highly expressed in these differentiated cells. All of these data indicated that we have successfully established a highly efficient differentiation protocol from hiPSCs to brown adipose tissue.
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Report
(1 results)
Research Products
(2 results)
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[Journal Article] Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice2021
Author(s)
Takenaka-Ninagawa N, Kima J, Zhao M, Sato M, Jonouchi T, Goto M, Yoshioka C, Ikeda R, Harada A, Sato T, Ikeya M, Uezumi A, Nakatani M, Noguchi S, Sakurai H
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Journal Title
Stem Cell Research & Therapy
Volume: 12
Pages: 446-446
DOI
NAID
Related Report
Peer Reviewed / Open Access
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