Bmi1 Regulates Wnt Signaling in Hematopoietic Stem and Progenitor Cells.
Hao YuRui GaoSisi ChenXicheng LiuQiang WangWenjie CaiSasidhar VemulaAidan C FaheyDanielle HenleyMichihiro KobayashiStephen Z LiuZhijian QianReuben KapurHal E BroxmeyerZhonghua GaoRongwen XiYan LiuPublished in: Stem cell reviews and reports (2021)
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.
Keyphrases
- signaling pathway
- body mass index
- cell proliferation
- induced apoptosis
- pi k akt
- stem cells
- genome wide
- weight gain
- gene expression
- epithelial mesenchymal transition
- genome wide identification
- hematopoietic stem cell
- cell cycle arrest
- dna methylation
- type diabetes
- transcription factor
- oxidative stress
- bioinformatics analysis
- risk assessment
- endoplasmic reticulum stress
- skeletal muscle
- mesenchymal stem cells
- climate change