Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells

Hao Yu, Rui Gao, Sisi Chen, Xicheng Liu, Qiang Wang, Wenjie Cai, Sasidhar Vemula, Aidan C. Fahey, Danielle Henley, Michihiro Kobayashi, Stephen Z. Liu, Zhijian Qian, Reuben Kapur, Hal E. Broxmeyer, Zhonghua Gao, Rongwen Xi, Yan Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-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. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)2304-2313
Number of pages10
JournalStem Cell Reviews and Reports
Volume17
Issue number6
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Cancer Research

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