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Signaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis.

TitleSignaling from the sympathetic nervous system regulates hematopoietic stem cell emergence during embryogenesis.
Publication TypeJournal Article
Year of Publication2012
AuthorsFitch SR, Kimber GM, Wilson NK, Parker A, Mirshekar-Syahkal B, Göttgens B, Medvinsky A, Dzierzak E, Ottersbach K
JournalCell Stem Cell
Volume11
Issue4
Pagination554-66
Date Published2012 Oct 5
ISSN1875-9777
KeywordsAdult Stem Cells, Animals, Aorta, Catecholamines, Cell Line, Embryo, Mammalian, Embryonic Development, GATA3 Transcription Factor, Gene Expression Regulation, Developmental, Gonads, Hematopoietic Stem Cells, Mesonephros, Mice, Mice, Knockout, Signal Transduction, Stem Cell Niche, Sympathetic Nervous System
Abstract

The first adult-repopulating hematopoietic stem cells (HSCs) emerge in the aorta-gonads-mesonephros (AGM) region of the embryo. We have recently identified the transcription factor Gata3 as being upregulated in this tissue specifically at the time of HSC emergence. We now demonstrate that the production of functional and phenotypic HSCs in the AGM is impaired in the absence of Gata3. Furthermore, we show that this effect on HSC generation is secondary to the role of Gata3 in the production of catecholamines, the mediators of the sympathetic nervous system (SNS), thus making these molecules key components of the AGM HSC niche. These findings demonstrate that the recently described functional interplay between the hematopoietic system and the SNS extends to the earliest stages of their codevelopment and highlight the fact that HSC development needs to be viewed in the context of the development of other organs.

DOI10.1016/j.stem.2012.07.002
Alternate JournalCell Stem Cell
PubMed ID23040481
PubMed Central IDPMC3510442
Grant List079249 / / Wellcome Trust / United Kingdom
G0500950 / / Medical Research Council / United Kingdom
G0800784 / / Medical Research Council / United Kingdom
G0900951 / / Medical Research Council / United Kingdom
G0900962 / / Medical Research Council / United Kingdom
R37 DK054077 / DK / NIDDK NIH HHS / United States
R37DK054077 / DK / NIDDK NIH HHS / United States
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