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Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling.

TitleIdentification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling.
Publication TypeJournal Article
Year of Publication2009
AuthorsMascarenhas MI, Parker A, Dzierzak E, Ottersbach K
JournalBlood
Volume114
Issue21
Pagination4645-53
Date Published2009 Nov 19
ISSN1528-0020
KeywordsAnimals, Aorta, Cell Differentiation, Embryo, Mammalian, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gonads, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunohistochemistry, In Situ Hybridization, Mesonephros, Mice, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction
Abstract

The first adult-repopulating hematopoietic stem cells (HSCs) are detected starting at day 10.5 of gestation in the aorta-gonads-mesonephros (AGM) region of the mouse embryo. Despite the importance of the AGM in initiating HSC production, very little is currently known about the regulators that control HSC emergence in this region. We have therefore further defined the location of HSCs in the AGM and incorporated this information into a spatial and temporal comparative gene expression analysis of the AGM. The comparisons included gene expression profiling (1) in the newly identified HSC-containing region compared with the region devoid of HSCs, (2) before and after HSC emergence in the AGM microenvironment, and (3) on populations enriched for HSCs and their putative precursors. Two genes found to be up-regulated at the time and place where HSCs are first detected, the cyclin-dependent kinase inhibitor p57Kip2/Cdkn1c and the insulin-like growth factor 2, were chosen for further analysis. We demonstrate here that they play a novel role in AGM hematopoiesis. Interestingly, many genes involved in the development of the tissues surrounding the dorsal aorta are also up-regulated during HSC emergence, suggesting that the regulation of HSC generation occurs in coordination with the development of other organs.

DOI10.1182/blood-2009-06-230037
Alternate JournalBlood
PubMed ID19794138
PubMed Central IDPMC2780301
Grant ListG0800784 / / Medical Research Council / United Kingdom
R37 DK054077 / DK / NIDDK NIH HHS / United States
R37 DK054077-09 / DK / NIDDK NIH HHS / United States
R37DK054077 / DK / NIDDK NIH HHS / United States
/ / Medical Research Council / United Kingdom
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