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Series GSE26086 Query DataSets for GSE26086
Status Public on Dec 21, 2010
Title HIF-1synergizes with glucocorticoids to promote BFU-E progenitor self-renewal
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design 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
Contributor(s) Flygare J, Estrada VR, Shin C, Gupta S, Lodish HF
Citation(s) 21177435
Submission date Dec 15, 2010
Last update date May 15, 2019
Contact name Whitehead Institute
Phone 617-324-0339
Organization name Whitehead Institute
Department Genome Technology Core
Street address 9 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02141
Country USA
Platforms (1)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (9)
GSM640429 BFU-E_RNA-Seq
GSM640430 CFU-E_RNA-Seq
GSM640431 Ter119+_RNA-Seq
SRA SRP005102
BioProject PRJNA135107

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26086_RAW.tar 1.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Processed data provided as supplementary file
Raw data are available in SRA

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