Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma

Yasumizu, Yoshiaki; Kinoshita, Makoto; Zhang, Martin Jinye; Motooka, Daisuke; Suzuki, Koichiro; Nojima, Satoshi; Koizumi, Naoshi; Okuzaki, Daisuke; Funaki, Soichiro; Shintani, Yasushi; Ohkura, Naganari; Morii, Eiichi; Okuno, Tatsusada; Mochizuki, Hideki

doi:https://doi.org/10.1016/j.celrep.2024.114677

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma

Yasumizu, Yoshiaki; Kinoshita, Makoto; Zhang, Martin Jinye et al.

Cell reports, 2024, 43(9), 114677

Number of Access:1,831（2025-07-18 12:53 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98360

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Title	Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
Creator	CreatorName Yasumizu, Yoshiaki
	NRID 1000010573222 1000010573222 researchmap permalink 101101101101101 101101101101101 Scopus Author ID 55363330100 55363330100 CreatorName Kinoshita, Makoto
	CreatorName Zhang, Martin Jinye
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 CreatorName Motooka, Daisuke
	researchmap permalink rad40775326 rad40775326 Scopus Author ID 57201054345 57201054345 CreatorName Suzuki, Koichiro
	NRID 1000040528791 1000040528791 ORCID 0000-0002-5124-0026 0000-0002-5124-0026 researchmap permalink snojima snojima Scopus Author ID 16224082000 16224082000 CreatorName Nojima, Satoshi
	CreatorName Koizumi, Naoshi
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000050464251 1000050464251 researchmap permalink so1 so1 Scopus Author ID 14123352700 14123352700 CreatorName Funaki, Soichiro
	NRID 1000090572983 1000090572983 researchmap permalink shintani6384 shintani6384 Scopus Author ID 7103142734 7103142734 CreatorName Shintani, Yasushi
	NRID 1000020300949 1000020300949 researchmap permalink read0007148 read0007148 Scopus Author ID 7004263301 7004263301 CreatorName Ohkura, Naganari
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 CreatorName Morii, Eiichi
	NRID 1000000464248 1000000464248 researchmap permalink neuroimmunology neuroimmunology Scopus Author ID 9736132000 9736132000 CreatorName Okuno, Tatsusada
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 CreatorName Mochizuki, Hideki
Subject	CP: Immunology
	ectopic lymphoid structure
	myasthenia gravis
	spatial transcriptome
	thymoma
Description	Yasumizu Y., Kinoshita M., Zhang M.J., et al. Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma. Cell reports 43, 114677 (2024); https://doi.org/10.1016/j.celrep.2024.114677.
Abstract	Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research.
Publisher	Cell Press
Source Title	Cell reports
Volume (Issue)	43(9)
Page	114677
Date of Issued	2024-09-24
Language	English
Handle URL	https://hdl.handle.net/11094/98360
eISSN	22111247
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.celrep.2024.114677
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cell reports. 2024, 43(9), p. 114677
DC.title	Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
DC.creator	Yasumizu, Yoshiaki
	Kinoshita, Makoto
	Zhang, Martin Jinye
	Motooka, Daisuke
	Suzuki, Koichiro
	Nojima, Satoshi
	Koizumi, Naoshi
	Okuzaki, Daisuke
	Funaki, Soichiro
	Shintani, Yasushi
	Ohkura, Naganari
	Morii, Eiichi
	Okuno, Tatsusada
	Mochizuki, Hideki
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-09-24
DC.identifier	https://doi.org/10.1016/j.celrep.2024.114677
DC.subject	CP: Immunology
	ectopic lymphoid structure
	myasthenia gravis
	spatial transcriptome
	thymoma
DC.description	Yasumizu Y., Kinoshita M., Zhang M.J., et al. Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma. Cell reports 43, 114677 (2024); https://doi.org/10.1016/j.celrep.2024.114677.
DCTERMS.abstract	Myasthenia gravis (MG) is etiologically associated with thymus abnormalities, but its pathology in the thymus remains unclear. In this study, we attempt to narrow down the features associated with MG using spatial transcriptome analysis of thymoma and thymic hyperplasia samples. We find that the majority of thymomas are constituted by the cortical region. However, the small medullary region is enlarged in seropositive thymomas and contains polygenic enrichment and MG-specific germinal center structures. Neuromuscular medullary thymic epithelial cells, previously identified as MG-specific autoantigen-producing cells, are enriched in the cortico-medullary junction. The medulla is characterized by a specific chemokine pattern and immune cell composition, including migratory dendritic cells and effector regulatory T cells. Similar germinal center structures and immune microenvironments are also observed in the thymic hyperplasia medulla. This study shows that the medulla and junction areas are linked to MG pathology and provides insights into future MG research.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98360
citation_title	Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
citation_author	Yasumizu, Yoshiaki
	Kinoshita, Makoto
	Zhang, Martin Jinye
	Motooka, Daisuke
	Suzuki, Koichiro
	Nojima, Satoshi
	Koizumi, Naoshi
	Okuzaki, Daisuke
	Funaki, Soichiro
	Shintani, Yasushi
	Ohkura, Naganari
	Morii, Eiichi
	Okuno, Tatsusada
	Mochizuki, Hideki
citation_publisher	Cell Press
citation_language	English
citation_date	2024-09-24
citation_journal_title	Cell reports
citation_volume	43
citation_issue	9
citation_firstpage	114677
citation_doi	https://doi.org/10.1016/j.celrep.2024.114677
citation_public_url	https://hdl.handle.net/11094/98360

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma

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