Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi

Kitano, Takaya; Sasaki, Tsutomu; Matsui, Takahiro; Kohara, Masaharu; Ogawa, Kotaro; Todo, Kenichi; Nakamura, Hajime; Sugiura, Yuri; Shimada, Yuki; Okazaki, Shuhei; Iida, Junichi; Shimazu, Kohki; Morii, Eiichi; Sakaguchi, Manabu; Nishio, Masami; Yokoe, Masaru; Kishima, Haruhiko; Mochizuki, Hideki

doi:https://doi.org/10.1161/JAHA.125.044299

Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi

Kitano, Takaya; Sasaki, Tsutomu; Matsui, Takahiro et al.

Journal of the American Heart Association, 2025, 14(19), e044299

アクセス数:503件（2026-02-05 15:52 集計）

固定URL: https://hdl.handle.net/11094/103280

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タイトル	Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi
著者	NRID 1000070772193 1000070772193 ORCID 0000-0003-1903-8255 0000-0003-1903-8255 researchmap permalink takayakitano takayakitano Scopus Author ID 57190440737 57190440737 著者名 Kitano, Takaya
	NRID 1000020534879 1000020534879 ORCID 0000-0001-8726-978X 0000-0001-8726-978X researchmap permalink tsutomusasaki1111 tsutomusasaki1111 Scopus Author ID 7407394272 7407394272 著者名 Sasaki, Tsutomu
	NRID 1000050747037 1000050747037 ORCID 0000-0002-6753-1688 0000-0002-6753-1688 researchmap permalink takahiromatsui takahiromatsui Scopus Author ID 35176152500 35176152500 著者名 Matsui, Takahiro
	NRID 1000000379257 1000000379257 ORCID 0009-0006-7636-5833 0009-0006-7636-5833 Scopus Author ID 22234528100 22234528100 著者名 Kohara, Masaharu
	NRID 1000080870500 1000080870500 ORCID 0000-0002-2566-7675 0000-0002-2566-7675 researchmap permalink jihdiegisojosugudc jihdiegisojosugudc Scopus Author ID 57200553653 57200553653 著者名 Ogawa, Kotaro
	著者名 Todo, Kenichi
	NRID 1000080533794 1000080533794 researchmap permalink hnns-osaka hnns-osaka Scopus Author ID 55624478238 55624478238 著者名 Nakamura, Hajime
	著者名 Sugiura, Yuri
	著者名 Shimada, Yuki
	NRID 1000060623072 1000060623072 researchmap permalink s-okazaki s-okazaki Scopus Author ID 16417354000 16417354000 著者名 Okazaki, Shuhei
	著者名 Iida, Junichi
	著者名 Shimazu, Kohki
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 著者名 Morii, Eiichi
	NRID 1000070432474 1000070432474 著者名 Sakaguchi, Manabu
	著者名 Nishio, Masami
	著者名 Yokoe, Masaru
	NRID 1000010332743 1000010332743 ORCID 0000-0002-9041-2337 0000-0002-9041-2337 researchmap permalink hkishima hkishima Scopus Author ID 6603783358 6603783358 著者名 Kishima, Haruhiko
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 著者名 Mochizuki, Hideki
キーワード等	extracellular matrix
	osteopontin
	RNA sequencing
	stroke
	thrombosis
内容	Kitano T., Sasaki T., Matsui T., et al. Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi. Journal of the American Heart Association 14(19), e044299 (2025); https://doi.org/10.1161/JAHA.125.044299.
抄録	BACKGROUND: Thrombi follow various natural courses. They are known to become harder over time and may persist long term; some of them can also undergo early spontaneous dissolution and disappearance. Hindering thrombus stability may contribute to the treatment of thrombosis and the prevention of embolisms. However, the detailed mechanisms underlying thrombus maturation remain unclear. METHODS: We compared the RNA expression in 3 thrombi retrieved from cerebral vessels via thrombectomy with that in simultaneously sampled blood. The results were validated using immunohistochemistry on 66 thrombi retrieved from patients with cerebral embolism. Single-cell RNA sequencing data of thrombi from pulmonary arteries were used to uncover the molecular mechanisms. RESULTS: A total of 1121 genes were upregulated in thrombi. Pathway enrichment and protein-protein interaction analyses revealed upregulation of extracellular matrix formation and identified SPP1 as a hub gene. Immunohistochemistry revealed that expression level of osteopontin (the transcript of SPP1) positively correlated to that of collagen type VI in thrombi. Osteopontin was expressed primarily by monocytes/macrophages in the thrombi, particularly in older ones. Among these 66 patients, the presence of collagen type VI in the thrombus was marginally associated with longer puncture-to-reperfusion time and more passes before reperfusion, indicating that those thrombi were resistant to thrombectomy. Single-cell RNA sequencing of thrombi identified a subpopulation of monocytes/macrophages that highly express SPP1. These SPP1-high monocytes/macrophages highly expressed genes related to the extracellular matrix and communicated closely with fibroblasts. CONCLUSIONS: Collectively, our findings indicate that SPP1-high monocytes/macrophages play a crucial role in thrombus maturation.
出版者	John Wiley and Sons Inc
収録物名	Journal of the American Heart Association
巻(号)	14(19)
ページ	e044299
刊行年月	2025-09-30
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103280
eISSN	20479980
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1161/JAHA.125.044299
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 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	Journal of the American Heart Association. 2025, 14(19), p. e044299
DC.title	Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi
DC.creator	Kitano, Takaya
	Sasaki, Tsutomu
	Matsui, Takahiro
	Kohara, Masaharu
	Ogawa, Kotaro
	Todo, Kenichi
	Nakamura, Hajime
	Sugiura, Yuri
	Shimada, Yuki
	Okazaki, Shuhei
	Iida, Junichi
	Shimazu, Kohki
	Morii, Eiichi
	Sakaguchi, Manabu
	Nishio, Masami
	Yokoe, Masaru
	Kishima, Haruhiko
	Mochizuki, Hideki
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-09-30
DC.identifier	https://doi.org/10.1161/JAHA.125.044299
DC.subject	extracellular matrix
	osteopontin
	RNA sequencing
	stroke
	thrombosis
DC.description	Kitano T., Sasaki T., Matsui T., et al. Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi. Journal of the American Heart Association 14(19), e044299 (2025); https://doi.org/10.1161/JAHA.125.044299.
DCTERMS.abstract	BACKGROUND: Thrombi follow various natural courses. They are known to become harder over time and may persist long term; some of them can also undergo early spontaneous dissolution and disappearance. Hindering thrombus stability may contribute to the treatment of thrombosis and the prevention of embolisms. However, the detailed mechanisms underlying thrombus maturation remain unclear. METHODS: We compared the RNA expression in 3 thrombi retrieved from cerebral vessels via thrombectomy with that in simultaneously sampled blood. The results were validated using immunohistochemistry on 66 thrombi retrieved from patients with cerebral embolism. Single-cell RNA sequencing data of thrombi from pulmonary arteries were used to uncover the molecular mechanisms. RESULTS: A total of 1121 genes were upregulated in thrombi. Pathway enrichment and protein-protein interaction analyses revealed upregulation of extracellular matrix formation and identified SPP1 as a hub gene. Immunohistochemistry revealed that expression level of osteopontin (the transcript of SPP1) positively correlated to that of collagen type VI in thrombi. Osteopontin was expressed primarily by monocytes/macrophages in the thrombi, particularly in older ones. Among these 66 patients, the presence of collagen type VI in the thrombus was marginally associated with longer puncture-to-reperfusion time and more passes before reperfusion, indicating that those thrombi were resistant to thrombectomy. Single-cell RNA sequencing of thrombi identified a subpopulation of monocytes/macrophages that highly express SPP1. These SPP1-high monocytes/macrophages highly expressed genes related to the extracellular matrix and communicated closely with fibroblasts. CONCLUSIONS: Collectively, our findings indicate that SPP1-high monocytes/macrophages play a crucial role in thrombus maturation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	103280
citation_title	Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi
citation_author	Kitano, Takaya
	Sasaki, Tsutomu
	Matsui, Takahiro
	Kohara, Masaharu
	Ogawa, Kotaro
	Todo, Kenichi
	Nakamura, Hajime
	Sugiura, Yuri
	Shimada, Yuki
	Okazaki, Shuhei
	Iida, Junichi
	Shimazu, Kohki
	Morii, Eiichi
	Sakaguchi, Manabu
	Nishio, Masami
	Yokoe, Masaru
	Kishima, Haruhiko
	Mochizuki, Hideki
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2025-09-30
citation_journal_title	Journal of the American Heart Association
citation_volume	14
citation_issue	19
citation_firstpage	e044299
citation_doi	https://doi.org/10.1161/JAHA.125.044299
citation_public_url	https://hdl.handle.net/11094/103280

Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi

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