Article

Alternative Runx1 promoter usage in mouse developmental hematopoiesis.

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
Blood Cells Molecules and Diseases (impact factor: 2.35). 43(1):35-42. DOI:10.1016/j.bcmd.2009.03.011 pp.35-42
Source: PubMed

ABSTRACT The interest in stem cell based therapies has emphasized the importance of understanding the cellular and molecular mechanisms by which stem cells are generated in ontogeny and maintained throughout adult life. Hematopoietic stem cells (HSCs) are first found in clusters of hematopoietic cells budding from the luminal wall of the major arteries in the developing mammalian embryo. The transcription factor Runx1 is critical for their generation and is specifically expressed at sites of HSC generation, prior to their formation. To understand better the transcriptional hierarchies that converge on Runx1 during HSC emergence, we have initiated studies into its transcriptional regulation. Here we systematically analyzed Runx1 P1 and P2 alternative promoter usage in hematopoietic sites and in sorted cell populations during mouse hematopoietic development. Our results indicate that Runx1 expression in primitive erythrocytes is largely P2-derived, whilst in definitive hematopoietic stem and/or progenitor cells from the yolk sac or AGM and vitelline and umbilical arteries both the distal P1 and proximal P2 promoters are active. After cells have migrated to the fetal liver, the P1 gradually becomes the main hematopoietic promoter and remains this into adulthood. In addition, we identified a novel P2-derived Runx1 isoform.

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Keywords

definitive hematopoietic
 
distal P1
 
fetal liver
 
hematopoietic cells
 
hematopoietic sites
 
HSC emergence
 
HSC generation
 
main hematopoietic promoter
 
mouse hematopoietic development
 
novel P2-derived Runx1 isoform
 
P2 alternative promoter usage
 
progenitor cells
 
proximal P2 promoters
 
Runx1 expression
 
stem cells
 
transcription factor Runx1
 
transcriptional hierarchies
 
transcriptional regulation
 
umbilical arteries
 
yolk sac