Journal
STEM CELL REVIEWS AND REPORTS
Volume 17, Issue 6, Pages 2304-2313Publisher
SPRINGER
DOI: 10.1007/s12015-021-10253-4
Keywords
Bmi1; HSC; Self-renewal; Differentiation; Wnt; And beta-catenin
Funding
- DoD [W81XWH-18-1-0265, W81XWH-19-1-0575]
- Leukemia & Lymphoma Society Translational Research Program award [6581-20]
- St. Baldrick's Foundation Scholar Award
- NIDDK Cooperative Center of Excellence in Hematology (CCEH) grant [U54 DK106846]
- Project Development Team within the ICTSI NIH/NCRR [UL1TR001108]
- [R01 HL150624]
- [R56 DK119524]
- [R56 AG052501]
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Bmi1 is identified as a novel regulator of the Wnt signaling pathway in HSPCs, repressing Wnt gene expression and impacting HSC self-renewal and differentiation. Modulating Wnt signaling may hold potential for enhancing HSC transplantation outcomes.
Polycomb group protein Bmi1 is essential for hematopoietic stem cell (HSC) self-renewal and terminal differentiation. However, its target genes in hematopoietic stem and progenitor cells are largely unknown. We performed gene expression profiling assays and found that genes of the Wnt signaling pathway are significantly elevated in Bmi1 null hematopoietic stem and progenitor cells (HSPCs). Bmi1 is associated with several genes of the Wnt signaling pathway in hematopoietic cells. Further, we found that Bmi1 represses Wnt gene expression in HSPCs. Importantly, loss of beta-catenin, which reduces Wnt activation, partially rescues the HSC self-renewal and differentiation defects seen in the Bmi1 null mice. Thus, we have identified Bmi1 as a novel regulator of Wnt signaling pathway in HSPCs. Given that Wnt signaling pathway plays an important role in hematopoiesis, our studies suggest that modulating Wnt signaling may hold potential for enhancing HSC self-renewal, thereby improving the outcomes of HSC transplantation.
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