Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells

Yamashita, Akihiro; Yoshitomi, Hiroyuki; Kihara, Shunsuke et al.

Stem Cells Translational Medicine, 2020, 10(1), 115-127

Number of Access:420（2025-09-01 13:10 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93302

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Title
Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells
Creator
NRID
1000000636855 1000000636855
researchmap permalink
Aki_yama26 Aki_yama26
Scopus Author ID
56404044900 56404044900
CreatorName
Yamashita, Akihiro
NRID
1000050402920 1000050402920
CreatorName
Yoshitomi, Hiroyuki
CreatorName
Kihara, Shunsuke
NRID
1000040273502 1000040273502
CreatorName
Toguchida, Junya
NRID
1000050303938 1000050303938
ORCID
0000-0002-0520-3654 0000-0002-0520-3654
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Scopus Author ID
7004069586 7004069586
CreatorName
Tsumaki, Noriyuki
Subject
cartilage
chondrocyte
chondrogenesis
differentiation
iPSCs
pluripotent stem cells
stem cell culture
Description
Yamashita A., Yoshitomi H., Kihara S., et al. Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells. Stem Cells Translational Medicine 10, 115 (2021); https://doi.org/10.1002/sctm.20-0058.
Abstract
Human induced pluripotent stem cells (hiPSCs) are a promising cell source for the creation of cartilage to treat articular cartilage damage. The molecular mechanisms that translate culture conditions to the chondrogenic differentiation of hiPSCs remain to be analyzed. To analyze the effects of culture substrates, we chondrogenically differentiated hiPSCs on Matrigel or laminin 511-E8 while holding the composition of the chondrogenic medium constant. Cartilage was formed from hiPSCs on Matrigel, but not on laminin 511-E8. On Matrigel, the hiPSCs were round and yes-associated protein (YAP) was inactive. In contrast, on laminin 511-E8, the hiPSCs were flat and YAP was active. Treating the laminin 511-E8 hiPSCs in a bioreactor caused cell aggregates, in which the cells were round and YAP was inactive. Subsequent culture of the aggregates in chondrogenic medium resulted in cartilage formation. Transient knockdown of YAP in hiPSCs around the start of chondrogenic differentiation successfully formed cartilage on laminin 511-E8, suggesting that the activation of YAP is responsible for the failure of cartilage formation from hiPSCs on laminin 511-E8. Consistently, the addition of YAP inhibitors to laminin 511-E8 hiPSCs caused partial cartilage formation. This study contributes to identifying the molecules that mediate the effects of culture substrates on the chondrogenic differentiation of hiPSCs as well as to developing clinically applicable chondrogenic differentiation methods.
Publisher
John Wiley and Sons Ltd
Source Title
Stem Cells Translational Medicine
Volume (Issue)
10(1)
Page
115-127
Date of Issued
2020-07-12
Language
English
Handle URL
https://hdl.handle.net/11094/93302
PISSN
21576564
eISSN
21576580
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1002/sctm.20-0058
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
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Version of Record
Category
学術雑誌論文 Journal Article