Convergence of hypoxia and TGFβ pathways on cell cycle regulation in human hematopoietic stem/progenitor cells.

ABSTRACT: Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia. Geneset enrichment analysis (GSEA) revealed that, besides known pathways associated with "hypoxia-induced signaling", also significant enrichment for the Transforming Growth Factor beta (TGFβ) pathway was observed within the hypoxia/HIF1/HIF2 transcriptomes. One of the

SUBMITTER: Wierenga AT 

PROVIDER: S-EPMC3970968 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature