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Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells

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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.

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Acknowledgements

This work was supported by R01 HL150624, R56 DK119524, R56 AG052501, DoD W81XWH-18-1-0265 and DoD W81XWH-19-1-0575 awards to YL. This work was supported in part by the Leukemia & Lymphoma Society Translational Research Program award 6581-20 and the St. Baldrick’s Foundation Scholar Award to YL. The authors would like to acknowledge the Flow Cytometry Core and In vivo Therapeutic Core Laboratories, which were sponsored, in part, by the NIDDK Cooperative Center of Excellence in Hematology (CCEH) grant U54 DK106846. This work was supported, in part, by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108.

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Author notes

  1. Hao Yu, Rui Gao and Sisi Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Hao Yu, Rui Gao, Wenjie Cai, Sasidhar Vemula, Aidan C. Fahey, Danielle Henley, Michihiro Kobayashi, Stephen Z. Liu, Reuben Kapur & Yan Liu

  2. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Sisi Chen & Yan Liu

  3. National Institute of Biological Science, Beijing, China

    Xicheng Liu & Rongwen Xi

  4. Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA, 17033, USA

    Qiang Wang & Zhonghua Gao

  5. Department of Medicine, University of Florida, Gainesville, FL, 32610, USA

    Zhijian Qian

  6. Department of Microbiology and Immunology, Indiana University, Indianapolis, IN, 46202, USA

    Hal E. Broxmeyer

  7. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Yan Liu

  8. Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA

    Yan Liu

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  1. Hao Yu
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Contributions

H.Y., R.G., S.C., R.X., and Y.L. Designed the research. H.Y., R.G., S.C., X.L., Q.W., W.C., S.V., A.C.F., D.H., M.K., and S.Z.L. Performed the research; H.Y., R.G., S.C., Q.W., and Y.L. Analyzed the data and performed the statistical analysis. Z.Q., R.K., H.E.B., and Z.G. Provided reagents and constructive advice to the study. S.C., R.X., and Y.L. Wrote the manuscript. All authors read, commented on, and approved the manuscript.

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Correspondence to Rongwen Xi or Yan Liu.

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Yu, H., Gao, R., Chen, S. et al. Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells. Stem Cell Rev and Rep 17, 2304–2313 (2021). https://doi.org/10.1007/s12015-021-10253-4

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