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

Yamashita, Akihiro; Yoshitomi, Hiroyuki; Kihara, Shunsuke; Toguchida, Junya; Tsumaki, Noriyuki

doi:https://doi.org/10.1002/sctm.20-0058

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

アクセス数:590件（2026-02-15 18:43 集計）

固定URL: https://hdl.handle.net/11094/93302

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タイトル	Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells
著者	NRID 1000000636855 1000000636855 researchmap permalink Aki_yama26 Aki_yama26 Scopus Author ID 56404044900 56404044900 著者名 Yamashita, Akihiro
	NRID 1000050402920 1000050402920 著者名 Yoshitomi, Hiroyuki
	著者名 Kihara, Shunsuke
	NRID 1000040273502 1000040273502 著者名 Toguchida, Junya
	NRID 1000050303938 1000050303938 ORCID 0000-0002-0520-3654 0000-0002-0520-3654 researchmap permalink cart cart Scopus Author ID 7004069586 7004069586 著者名 Tsumaki, Noriyuki
キーワード等	cartilage
	chondrocyte
	chondrogenesis
	differentiation
	iPSCs
	pluripotent stem cells
	stem cell culture
内容	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.
抄録	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.
出版者	John Wiley and Sons Ltd
収録物名	Stem Cells Translational Medicine
巻(号)	10(1)
ページ	115-127
刊行年月	2020-07-12
言語	英語
ハンドルURL	https://hdl.handle.net/11094/93302
PISSN	21576564
eISSN	21576580
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/sctm.20-0058
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Stem Cells Translational Medicine. 2020, 10(1), p. 115-127
DC.title	Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells
DC.creator	Yamashita, Akihiro
	Yoshitomi, Hiroyuki
	Kihara, Shunsuke
	Toguchida, Junya
	Tsumaki, Noriyuki
DC.publisher	John Wiley and Sons Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-07-12
DC.identifier	https://doi.org/10.1002/sctm.20-0058
DC.subject	cartilage
	chondrocyte
	chondrogenesis
	differentiation
	iPSCs
	pluripotent stem cells
	stem cell culture
DC.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.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93302
citation_title	Culture substrate-associated YAP inactivation underlies chondrogenic differentiation of human induced pluripotent stem cells
citation_author	Yamashita, Akihiro
	Yoshitomi, Hiroyuki
	Kihara, Shunsuke
	Toguchida, Junya
	Tsumaki, Noriyuki
citation_publisher	John Wiley and Sons Ltd
citation_language	英語
citation_date	2020-07-12
citation_journal_title	Stem Cells Translational Medicine
citation_volume	10
citation_issue	1
citation_firstpage	115
citation_lastpage	127
citation_doi	https://doi.org/10.1002/sctm.20-0058
citation_public_url	https://hdl.handle.net/11094/93302

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

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