The transcriptional landscape of hematopoietic stem cell ontogeny.

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State: Public
Version: Author's accepted manuscript
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_BD9D4271C5A5
Type
Article: article from journal or magazin.
Collection
Publications
Title
The transcriptional landscape of hematopoietic stem cell ontogeny.
Journal
Cell stem cell
Author(s)
McKinney-Freeman S., Cahan P., Li H., Lacadie S.A., Huang H.T., Curran M., Loewer S., Naveiras O., Kathrein K.L., Konantz M., Langdon E.M., Lengerke C., Zon L.I., Collins J.J., Daley G.Q.
ISSN
1875-9777 (Electronic)
ISSN-L
1875-9777
Publication state
Published
Issued date
02/11/2012
Peer-reviewed
Oui
Volume
11
Number
5
Pages
701-714
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Transcriptome analysis of adult hematopoietic stem cells (HSCs) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSCs purified from >2,500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network-biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knockdown in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSCs, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification.
Keywords
Animals, Cell Differentiation, Embryonic Stem Cells/cytology, Embryonic Stem Cells/metabolism, Gene Expression Profiling, Hematopoietic Stem Cells/cytology, Hematopoietic Stem Cells/metabolism, Mice, Yolk Sac/cytology, Zebrafish
Pubmed
Web of science
Open Access
Yes
Create date
22/04/2022 16:53
Last modification date
08/10/2022 5:36
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