Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells

Matsumoto, Kenji; Isagawa, Takayuki; Nishimura, Toshinobu; Ogaeri, Takunori; Eto, Koji; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Aburatani, Hiroyuki; Nakauchi, Hiromitsu; Ema, Hideo

doi:https://doi.org/10.1371/journal.pone.0004820

Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells

Matsumoto, Kenji; Isagawa, Takayuki; Nishimura, Toshinobu et al.

PLoS ONE, 2009, 4(3), e4820-1-e4820-10

アクセス数:1,070件（2025-07-06 07:09 集計）

固定URL: https://hdl.handle.net/11094/23117

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タイトル	Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells
著者	NRID 1000060288701 1000060288701 著者名 Matsumoto, Kenji
	NRID 1000040418637 1000040418637 著者名 Isagawa, Takayuki
	著者名 Nishimura, Toshinobu
	NRID 1000070548776 1000070548776 著者名 Ogaeri, Takunori
	NRID 1000050286986 1000050286986 著者名 Eto, Koji
	NRID 1000060452439 1000060452439 ORCID 0000-0003-1781-1590 0000-0003-1781-1590 researchmap permalink satsuki satsuki Scopus Author ID 7401543503 7401543503 著者名 Miyazaki, Satsuki
	NRID 1000080229830 1000080229830 著者名 Miyazaki, Jun-ichi
	NRID 1000010202657 1000010202657 著者名 Aburatani, Hiroyuki
	NRID 1000040175485 1000040175485 著者名 Nakauchi, Hiromitsu
	NRID 1000050344445 1000050344445 著者名 Ema, Hideo
抄録	The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit+CD41+CD45− phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.
出版者	Public Library of Science
収録物名	PLoS ONE
巻(号)	4(3)
ページ	e4820-1-e4820-10
刊行年月	2009-03-16
言語	英語
ハンドルURL	https://hdl.handle.net/11094/23117
eISSN	19326203
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1371/journal.pone.0004820
アクセス権	open access
権利情報	© 2009 Matsumoto et al. This article is licensed under a Creative Commons Attribution 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	PLoS ONE. 2009, 4(3), p. e4820-1-e4820-10
DC.title	Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells
DC.creator	Matsumoto, Kenji
	Isagawa, Takayuki
	Nishimura, Toshinobu
	Ogaeri, Takunori
	Eto, Koji
	Miyazaki, Satsuki
	Miyazaki, Jun-ichi
	Aburatani, Hiroyuki
	Nakauchi, Hiromitsu
	Ema, Hideo
DC.publisher	Public Library of Science
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2009-03-16
DC.identifier	https://doi.org/10.1371/journal.pone.0004820
DCTERMS.abstract	The cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit+CD41+CD45− phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.
DC.rights	© 2009 Matsumoto et al. This article is licensed under a Creative Commons Attribution License.
DC.format	23117
citation_title	Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells
citation_author	Matsumoto, Kenji
	Isagawa, Takayuki
	Nishimura, Toshinobu
	Ogaeri, Takunori
	Eto, Koji
	Miyazaki, Satsuki
	Miyazaki, Jun-ichi
	Aburatani, Hiroyuki
	Nakauchi, Hiromitsu
	Ema, Hideo
citation_publisher	Public Library of Science
citation_language	英語
citation_date	2009-03-16
citation_journal_title	PLoS ONE
citation_volume	4
citation_issue	3
citation_firstpage	e4820-1
citation_lastpage	e4820-10
citation_doi	https://doi.org/10.1371/journal.pone.0004820
citation_public_url	https://hdl.handle.net/11094/23117

Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells

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