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:info:doi/10.1371/journal.pone.0004820

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タイトル	Stepwise development of Hematopoietic stem Cells from Embryonic Stem Cells
著者	Matsumoto, Kenji Matsumoto, Kenji
	Isagawa, Takayuki Isagawa, Takayuki
	Nishimura, Toshinobu Nishimura, Toshinobu
	Ogaeri, Takunori Ogaeri, Takunori
	Eto, Koji Eto, Koji
	Miyazaki, Satsuki Miyazaki, Satsuki
	Miyazaki, Jun-ichi Miyazaki, Jun-ichi
	Aburatani, Hiroyuki Aburatani, Hiroyuki
	Nakauchi, Hiromitsu Nakauchi, Hiromitsu
	Ema, Hideo 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.
公開者	Public Library of Science
掲載誌名	PLoS ONE
巻	4
号	3
開始ページ	e4820-1
終了ページ	e4820-10
刊行年月	2009-03-16
ISSN	19326203
DOI (出版社版)	info:doi/10.1371/journal.pone.0004820
URL	http://hdl.handle.net/11094/23117
権利情報	Copyright © 2009 Matsumoto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII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.4(3) P.e4820-1-P.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
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2009-03-16
DC.identifier	info:doi/10.1371/journal.pone.0004820
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23117
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	Copyright © 2009 Matsumoto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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_issn	19326203
citation_doi	info:doi/10.1371/journal.pone.0004820
citation_public_url	http://hdl.handle.net/11094/23117

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