Survivin modulates genes with divergent molecular functions and regulates proliferation of hematopoietic stem cells through Evi-1.

ABSTRACT: The inhibitor of apoptosis protein Survivin regulates hematopoiesis, although its mechanisms of regulation of hematopoietic stem cells (HSCs) remain largely unknown. While investigating conditional Survivin deletion in mice, we found that Survivin was highly expressed in phenotypically defined HSCs, and Survivin deletion in mice resulted in significantly reduced total marrow HSCs and hematopoietic progenitor cells. Transcriptional analysis of Survivin(-/-) HSCs revealed altered expression of multiple genes not previously linked to Survivin activity. In particular, Survivin deletion significantly reduced expression of the Evi-1 transcription factor indispensable for HSC function, and the downstream Evi-1 target genes Gata2, Pbx1 and Sall2. The loss of HSCs following Survivin deletion and im

SUBMITTER: Fukuda S 

PROVIDER: S-EPMC4258188 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature