TY - JOUR
T1 - Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells
AU - Yu, Hao
AU - Gao, Rui
AU - Chen, Sisi
AU - Liu, Xicheng
AU - Wang, Qiang
AU - Cai, Wenjie
AU - Vemula, Sasidhar
AU - Fahey, Aidan C.
AU - Henley, Danielle
AU - Kobayashi, Michihiro
AU - Liu, Stephen Z.
AU - Qian, Zhijian
AU - Kapur, Reuben
AU - Broxmeyer, Hal E.
AU - Gao, Zhonghua
AU - Xi, Rongwen
AU - Liu, Yan
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/12
Y1 - 2021/12
N2 - 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.]
AB - 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.]
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U2 - 10.1007/s12015-021-10253-4
DO - 10.1007/s12015-021-10253-4
M3 - Article
C2 - 34561772
AN - SCOPUS:85115632714
SN - 2629-3269
VL - 17
SP - 2304
EP - 2313
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 6
ER -