Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes

Hata, Kenji; Wakamori, Kanta; Hirakawa-Yamamura, Akane; Ichiyama-Kobayashi, Sachi; Yamaguchi, Masaya; Okuzaki, Daisuke; Takahata, Yoshifumi; Murakami, Tomohiko; Uzawa, Narikazu; Yamashiro, Takashi; Nishimura, Riko

doi:https://doi.org/10.1002/jcp.31490

Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes

Hata, Kenji; Wakamori, Kanta; Hirakawa-Yamamura, Akane et al.

Journal of Cellular Physiology, 2024, 240(1), e31490

アクセス数:1,731件（2025-07-29 15:43 集計）

固定URL: https://hdl.handle.net/11094/98515

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タイトル	Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes
著者	NRID 1000080444496 1000080444496 ORCID 0000-0003-4367-9343 0000-0003-4367-9343 researchmap permalink read0107167 read0107167 Scopus Author ID 8952419300 8952419300 著者名 Hata, Kenji
	著者名 Wakamori, Kanta
	著者名 Hirakawa-Yamamura, Akane
	著者名 Ichiyama-Kobayashi, Sachi
	NRID 1000000714536 1000000714536 ORCID 0000-0001-6218-7112 0000-0001-6218-7112 researchmap permalink MasayaYamaguchi MasayaYamaguchi Scopus Author ID 16074710900 16074710900 著者名 Yamaguchi, Masaya
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 著者名 Okuzaki, Daisuke
	NRID 1000060635845 1000060635845 researchmap permalink yoshifumitakahata yoshifumitakahata Scopus Author ID 22837135800 22837135800 ORCID 0000-0002-3322-0515 0000-0002-3322-0515 著者名 Takahata, Yoshifumi
	NRID 1000050510723 1000050510723 researchmap permalink read0139290 read0139290 Scopus Author ID 8509095600 8509095600 著者名 Murakami, Tomohiko
	NRID 1000030345285 1000030345285 researchmap permalink read0212957 read0212957 Scopus Author ID 6603144046 6603144046 著者名 Uzawa, Narikazu
	NRID 1000070294428 1000070294428 ORCID 0000-0002-4419-9643 0000-0002-4419-9643 researchmap permalink read0051793 read0051793 Scopus Author ID 55416765600 55416765600 著者名 Yamashiro, Takashi
	NRID 1000060294112 1000060294112 ORCID 0000-0001-7279-8363 0000-0001-7279-8363 researchmap permalink MolBiology MolBiology Scopus Author ID 7201418320 7201418320 著者名 Nishimura, Riko
キーワード等	growth plate chondrocyte
	pre-hypertrophic chondrocyte
	Serinc5
	single-cell RNA-seq
	Sox9
内容	Hata K., Wakamori K., Hirakawa-Yamamura A., et al. Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes. Journal of Cellular Physiology, (2024); https://doi.org/10.1002/jcp.31490.
抄録	The growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre-hypertrophic, and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate. However, the molecular basis of pre-hypertrophic chondrocytes remains largely undefined. Here, we employed scRNA-seq analysis on fluorescently labeled growth plate chondrocytes for their molecular characterization. Serine incorporator 5 (Serinc5) was identified as a marker gene for pre-hypertrophic chondrocytes. Histological analysis revealed that Serinc5 is specifically expressed in pre-hypertrophic chondrocytes, overlapping with Indian hedgehog (Ihh). Serinc5 represses cell proliferation and Col2a1 and Acan expression by inhibiting the transcriptional activity of Sox9 in primary chondrocytes. Chromatin profiling using ChIP-seq and ATAC-seq revealed an active enhancer of Serinc5 located in intron 1, with its chromatin status progressively activated during chondrocyte differentiation. Collectively, our findings suggest that Serinc5 regulates sequential chondrocyte differentiation from proliferation to hypertrophy by inhibiting Sox9 function in pre-hypertrophic chondrocytes, providing novel insights into the mechanisms underlying chondrocyte differentiation in growth plates.
出版者	John Wiley and Sons Inc
収録物名	Journal of Cellular Physiology
巻(号)	240(1)
ページ	e31490
刊行年月	2024-11-20
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98515
PISSN	00219541
eISSN	10974652
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/jcp.31490
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 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
DCTERMS.bibliographicCitation	Journal of Cellular Physiology. 2024, 240(1), p. e31490
DC.title	Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes
DC.creator	Hata, Kenji
	Wakamori, Kanta
	Hirakawa-Yamamura, Akane
	Ichiyama-Kobayashi, Sachi
	Yamaguchi, Masaya
	Okuzaki, Daisuke
	Takahata, Yoshifumi
	Murakami, Tomohiko
	Uzawa, Narikazu
	Yamashiro, Takashi
	Nishimura, Riko
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-11-20
DC.identifier	https://doi.org/10.1002/jcp.31490
DC.subject	growth plate chondrocyte
	pre-hypertrophic chondrocyte
	Serinc5
	single-cell RNA-seq
	Sox9
DC.description	Hata K., Wakamori K., Hirakawa-Yamamura A., et al. Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes. Journal of Cellular Physiology, (2024); https://doi.org/10.1002/jcp.31490.
DCTERMS.abstract	The growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre-hypertrophic, and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate. However, the molecular basis of pre-hypertrophic chondrocytes remains largely undefined. Here, we employed scRNA-seq analysis on fluorescently labeled growth plate chondrocytes for their molecular characterization. Serine incorporator 5 (Serinc5) was identified as a marker gene for pre-hypertrophic chondrocytes. Histological analysis revealed that Serinc5 is specifically expressed in pre-hypertrophic chondrocytes, overlapping with Indian hedgehog (Ihh). Serinc5 represses cell proliferation and Col2a1 and Acan expression by inhibiting the transcriptional activity of Sox9 in primary chondrocytes. Chromatin profiling using ChIP-seq and ATAC-seq revealed an active enhancer of Serinc5 located in intron 1, with its chromatin status progressively activated during chondrocyte differentiation. Collectively, our findings suggest that Serinc5 regulates sequential chondrocyte differentiation from proliferation to hypertrophy by inhibiting Sox9 function in pre-hypertrophic chondrocytes, providing novel insights into the mechanisms underlying chondrocyte differentiation in growth plates.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98515
citation_title	Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes
citation_author	Hata, Kenji
	Wakamori, Kanta
	Hirakawa-Yamamura, Akane
	Ichiyama-Kobayashi, Sachi
	Yamaguchi, Masaya
	Okuzaki, Daisuke
	Takahata, Yoshifumi
	Murakami, Tomohiko
	Uzawa, Narikazu
	Yamashiro, Takashi
	Nishimura, Riko
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2024-11-20
citation_journal_title	Journal of Cellular Physiology
citation_volume	240
citation_issue	1
citation_firstpage	e31490
citation_doi	https://doi.org/10.1002/jcp.31490
citation_public_url	https://hdl.handle.net/11094/98515

Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes

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