title: Apc regulates the function of hematopoietic stem cells largely through β-catenin-dependent mechanisms.
abstract: Emerging evidence suggests that adenomatous polyposis coli (Apc) plays a critical role in the maintenance of hematopoietic stem/progenitor cells (HSCs/HPCs). The molecular pathways responsible for the function of Apc in HSCs/HPCs remain unclear. By genetic approach, we demonstrated that inactivation of β-catenin rescued the exhaustion of Apc-deficient HSCs/HPCs, thereby preventing bone marrow failure in Apc-deficient mice. β-catenin loss inhibited the excessive proliferation and apoptosis of Apc-deficient HSCs/HPCs, as well as their defects in myeloid and erythroid differentiation. In addition, loss of β-catenin reversed the down-regulation of Cdkn1a, Cdkn1b, and Mcl1 induced by Apc ablation in Lin(-)Sca(+)c-Kit(+). In assays of long-term stem cell function, the HSCs with deficiency of both Apc and β-catenin displayed a significantly enhanced self-renewal capacity compared with β-catenin-deficient and control HSCs. Our findings suggest that Apc regulates the survival, proliferation, and differentiation of HSCs/HPCs largely through a β-catenin-mediated pathway. They also indicate that multiple downstream targets of Apc including β-catenin may coordinately regulate HSC self-renewal.
authors.affiliation: Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Wenshu
authors.initials: W
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.forename: Ming
authors.initials: M
authors.lastname: Ming
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.forename: Amber
authors.initials: A
authors.lastname: Seba
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Qian
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D051176:beta Catenin
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