Gene Set: WIERENGA_STAT5A_TARGETS_UP

Standard name WIERENGA_STAT5A_TARGETS_UP
Systematic name M2210
Brief description Genes up-regulated in CD34+ [GeneID=947] cells by intermediate activity levels of STAT5A [GeneID=6776]; predominant long-term growth and self-renewal phenotype.
Full description or abstract The level of transcription factor activity critically regulates cell fate decisions, such as hematopoietic stem cell (HSC) self-renewal and differentiation. We introduced STAT5A transcriptional activity into human HSCs/progenitor cells in a dose-dependent manner by overexpression of a tamoxifen-inducible STAT5A(1*6)-estrogen receptor fusion protein. Induction of STAT5A activity in CD34(+) cells resulted in impaired myelopoiesis and induction of erythropoiesis, which was most pronounced at the highest STAT5A transactivation levels. In contrast, intermediate STAT5A activity levels resulted in the most pronounced proliferative advantage of CD34(+) cells. This coincided with increased cobblestone area-forming cell and long-term-culture-initiating cell frequencies, which were predominantly elevated at intermediate STAT5A activity levels but not at high STAT5A levels. Self-renewal of progenitors was addressed by serial replating of CFU, and only progenitors containing intermediate STAT5A activity levels contained self-renewal capacity. By extensive gene expression profiling we could identify gene expression patterns of STAT5 target genes that predominantly associated with a self-renewal and long-term expansion phenotype versus those that identified a predominant differentiation phenotype.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18779318   Authors: Wierenga AT,Vellenga E,Schuringa JJ
Exact source Table 2S: Fold change STAT3A(1*6)-ER > 1
Related gene sets (show 4 additional gene sets from the source publication)

(show 11 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Human_RefSeq
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Version history 3.1: First introduced

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