|
| 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.
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| |
|
| 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 |
| E-mail(s) |
sgupta@wi.mit.edu
|
| 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)
|
| GSM640432 |
BFU-E_CD71_4h_100nMDex_RNA-Seq |
| GSM640433 |
BFU-E_CD71_4h_Dexnegative_RNA-Seq |
| GSM640434 |
BFU-E_CD71-24_4h_100nMDex_RNA-Seq |
| GSM640435 |
BFU-E_CD71-24_4h_Negative_RNA-Seq |
| GSM640436 |
BFU-E_CD71-24_4h_100nMDex_333uMDMOG_RNA-Seq |
| GSM640437 |
BFU-E_CD71-24_4h_333uMDMOG_RNA-Seq |
|
| Relations |
| SRA |
SRP005102 |
| BioProject |
PRJNA135107 |
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