In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation

The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-...

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Main Authors:	Pearson, Stella, Cuvertino, Sara, Fleury, Maud, Lacaud, Georges, Kouskoff, Valerie
Format:	Online
Language:	English
Published:	Elsevier 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375940/

id	pubmed-4375940
recordtype	oai_dc
spelling	pubmed-43759402015-04-03 In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation Pearson, Stella Cuvertino, Sara Fleury, Maud Lacaud, Georges Kouskoff, Valerie Article The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in the absence of ectopically expressed factors. We show that repopulating activity arises immediately upon the commitment of mesodermal precursors to the blood program, within the first wave of hematopoietic specification. We establish that the formation of these progenitors is extremely transient and exquisitely sensitive to the cytokine milieu. Our findings define the precise differentiating stage at which hematopoietic repopulating activity first appears in vitro, and suggest that during embryonic stem cell differentiation, all hematopoietic programs are unraveled simultaneously from the mesoderm in the absence of cues that restrict the coordinated emergence of each lineage as is normally observed during embryogenesis. Elsevier 2015-02-05 /pmc/articles/PMC4375940/ /pubmed/25660408 http://dx.doi.org/10.1016/j.stemcr.2015.01.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Pearson, Stella Cuvertino, Sara Fleury, Maud Lacaud, Georges Kouskoff, Valerie
spellingShingle	Pearson, Stella Cuvertino, Sara Fleury, Maud Lacaud, Georges Kouskoff, Valerie In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
author_facet	Pearson, Stella Cuvertino, Sara Fleury, Maud Lacaud, Georges Kouskoff, Valerie
author_sort	Pearson, Stella
title	In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
title_short	In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
title_full	In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
title_fullStr	In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
title_full_unstemmed	In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation
title_sort	in vivo repopulating activity emerges at the onset of hematopoietic specification during embryonic stem cell differentiation
description	The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in the absence of ectopically expressed factors. We show that repopulating activity arises immediately upon the commitment of mesodermal precursors to the blood program, within the first wave of hematopoietic specification. We establish that the formation of these progenitors is extremely transient and exquisitely sensitive to the cytokine milieu. Our findings define the precise differentiating stage at which hematopoietic repopulating activity first appears in vitro, and suggest that during embryonic stem cell differentiation, all hematopoietic programs are unraveled simultaneously from the mesoderm in the absence of cues that restrict the coordinated emergence of each lineage as is normally observed during embryogenesis.
publisher	Elsevier
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375940/
_version_	1613204213006860288

In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation

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