Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

Nakatani, Taichi; Sugiyama, Tatsuki; Omatsu, Yoshiki; Watanabe, Hitomi; Kondoh, Gen; Nagasawa, Takashi

doi:https://doi.org/10.1038/s41467-023-42047-2

Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

Nakatani, Taichi; Sugiyama, Tatsuki; Omatsu, Yoshiki et al.

Nature Communications, 2023, 14(1), 6402

Number of Access:562（2025-07-25 21:15 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93240

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Title	Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells
Creator	CreatorName Nakatani, Taichi
	NRID 1000010456791 1000010456791 CreatorName Sugiyama, Tatsuki
	NRID 1000080437277 1000080437277 ORCID 0000-0002-6212-0441 0000-0002-6212-0441 researchmap permalink yskomt yskomt Scopus Author ID 6602904662 6602904662 CreatorName Omatsu, Yoshiki
	NRID 1000080624056 1000080624056 CreatorName Watanabe, Hitomi
	NRID 1000040243258 1000040243258 CreatorName Kondoh, Gen
	NRID 1000080281690 1000080281690 ORCID 0000-0002-1085-0960 0000-0002-1085-0960 researchmap permalink read0094728 read0094728 Scopus Author ID 35196507500 35196507500 CreatorName Nagasawa, Takashi
Description	Nakatani T., Sugiyama T., Omatsu Y., et al. Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells. Nature Communications 14, 6402 (2023); https://doi.org/10.1038/s41467-023-42047-2.
Abstract	Lympho-hematopoiesis is regulated by cytokines; however, it remains unclear how cytokines regulate hematopoietic stem cells (HSCs) to induce production of lymphoid progenitors. Here, we show that in mice whose CXC chemokine ligand 12 (CXCL12) is deleted from half HSC niche cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, HSCs migrate from CXCL12-deficient niches to CXCL12-intact niches. In mice whose CXCL12 is deleted from all Ebf3+/leptin receptor (LepR)+ CAR cells, HSCs are markedly reduced and their ability to generate B cell progenitors is reduced compared with that to generate myeloid progenitors even when transplanted into wild-type mice. Additionally, CXCL12 enables the maintenance of B lineage repopulating ability of HSCs in vitro. These results demonstrate that CAR cell-derived CXCL12 attracts HSCs to CAR cells within bone marrow and plays a critical role in the maintenance of HSCs, especially lymphoid-biased or balanced HSCs. This study suggests an additional mechanism by which cytokines act on HSCs to produce B cells.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	14(1)
Page	6402
Date of Issued	2023-10-25
Language	English
Handle URL	https://hdl.handle.net/11094/93240
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-023-42047-2
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
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2023, 14(1), p. 6402
DC.title	Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells
DC.creator	Nakatani, Taichi
	Sugiyama, Tatsuki
	Omatsu, Yoshiki
	Watanabe, Hitomi
	Kondoh, Gen
	Nagasawa, Takashi
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-10-25
DC.identifier	https://doi.org/10.1038/s41467-023-42047-2
DC.description	Nakatani T., Sugiyama T., Omatsu Y., et al. Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells. Nature Communications 14, 6402 (2023); https://doi.org/10.1038/s41467-023-42047-2.
DCTERMS.abstract	Lympho-hematopoiesis is regulated by cytokines; however, it remains unclear how cytokines regulate hematopoietic stem cells (HSCs) to induce production of lymphoid progenitors. Here, we show that in mice whose CXC chemokine ligand 12 (CXCL12) is deleted from half HSC niche cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, HSCs migrate from CXCL12-deficient niches to CXCL12-intact niches. In mice whose CXCL12 is deleted from all Ebf3+/leptin receptor (LepR)+ CAR cells, HSCs are markedly reduced and their ability to generate B cell progenitors is reduced compared with that to generate myeloid progenitors even when transplanted into wild-type mice. Additionally, CXCL12 enables the maintenance of B lineage repopulating ability of HSCs in vitro. These results demonstrate that CAR cell-derived CXCL12 attracts HSCs to CAR cells within bone marrow and plays a critical role in the maintenance of HSCs, especially lymphoid-biased or balanced HSCs. This study suggests an additional mechanism by which cytokines act on HSCs to produce B cells.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93240
citation_title	Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells
citation_author	Nakatani, Taichi
	Sugiyama, Tatsuki
	Omatsu, Yoshiki
	Watanabe, Hitomi
	Kondoh, Gen
	Nagasawa, Takashi
citation_publisher	Nature Research
citation_language	English
citation_date	2023-10-25
citation_journal_title	Nature Communications
citation_volume	14
citation_issue	1
citation_firstpage	6402
citation_doi	https://doi.org/10.1038/s41467-023-42047-2
citation_public_url	https://hdl.handle.net/11094/93240

Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

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