Transcriptomics

Dataset Information

301

HIF-1synergizes with glucocorticoids to promote BFU-E progenitor self-renewal


ABSTRACT: With the aim of finding small molecules that stimulate erythropoiesis earlier than erythropoietin and that enhance CFU-E production, we studied the mechanism by which glucocorticoids increase CFU-E formation. Using BFU-E and CFU-E progenitors purified by a new technique, we demonstrate that glucocorticoids stimulate the earliest (BFU-E) progenitors to undergo limited self-renewal, which increases formation of CFU-E cells > 20-fold. Interestingly, glucocorticoids induce expression of genes in BFU-E cells that contain promoter regions highly enriched for hypoxia-induced factor 1 alpha (HIF1a) binding sites. This suggests activation of HIF1a may enhance or replace the effect of glucocorticoids on BFU-E self-renewal. Indeed, HIF1a activation by a prolyl hydroxylase inhibitor (PHI) synergizes with glucocorticoids and enhances production of CFU-Es 170-fold. Since PHIs are able to increase erythroblast production at very low concentrations of glucocorticoids, PHI-induced stimulation of BFU-E progenitors thus represents a conceptually new therapeutic window for treating Epo-resistant anemia. RNA-Seq was performed on enriched populations of BFU-E, CFU-E and Ter119+ as well as BFU-E enriched cells treated with Dex and DMOG

ORGANISM(S): Mus musculus  

SUBMITTER: Violeta R Estrada   Harvey F Lodish  Johan Flygare  Sumeet Gupta  Whitehead Institute  Chanseok Shin 

PROVIDER: E-GEOD-26086 | ArrayExpress | 2010-12-21

SECONDARY ACCESSION(S): GSE26086SRP005102PRJNA135107

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

HIF1alpha synergizes with glucocorticoids to promote BFU-E progenitor self-renewal.

Flygare Johan J   Rayon Estrada Violeta V   Shin Chanseok C   Gupta Sumeet S   Lodish Harvey F HF  

Blood 20101221 12


With the aim of finding small molecules that stimulate erythropoiesis earlier than erythropoietin and that enhance erythroid colony-forming unit (CFU-E) production, we studied the mechanism by which glucocorticoids increase CFU-E formation. Using erythroid burst-forming unit (BFU-E) and CFU-E progenitors purified by a new technique, we demonstrate that glucocorticoids stimulate the earliest (BFU-E) progenitors to undergo limited self-renewal, which increases formation of CFU-E cells > 20-fold. I  ...[more]

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