APC/CCdh1 regulates the balance between maintenance and differentiation of hematopoietic stem and progenitor cells.
Hematopoietic stem and progenitor cells (HSPCs) represent the lifelong source of all blood cells and continuously regenerate the hematopoietic system through differentiation and self-renewal. The process of differentiation is initiated in the G1 phase of the cell cycle, when stem cells leave their quiescent state. During G1, the anaphase-promoting complex or cyclosome associated with the coactivator Cdh1 is highly active and marks proteins for proteasomal degradation to regulate cell proliferation. Following Cdh1 knockdown in HSPCs, we analyzed human and mouse hematopoiesis in vitro and in vivo in competitive transplantation assays. We found that Cdh1 is highly expressed in human CD34+ HSPCs and downregulated in differentiated subsets; whereas, loss of Cdh1 restricts myeloid differentiation, supports B cell development and preserves immature short-term HSPCs without affecting proliferation or viability. Our data highlight a role of Cdh1 as a regulator of balancing the maintenance of HSPCs and differentiation into mature blood cells.
['Ewerth|Daniel|D|', 'Kreutmair|Stefanie|S|', 'Schmidts|Andrea|A|', 'Ihorst|Gabriele|G|', 'Follo|Marie|M|', 'Wider|Dagmar|D|', 'Felthaus|Julia|J|', 'Schüler|Julia|J|', 'Duyster|Justus|J|', 'Illert|Anna Lena|AL|', 'Engelhardt|Monika|M|', 'Wäsch|Ralph|R|']
D000818:Animals D018952:Antigens, CD34 D001854:Bone Marrow Cells D064200:Cdh1 Proteins D002454:Cell Differentiation D049109:Cell Proliferation D006412:Hematopoietic Stem Cells D006801:Humans D051379:Mice D008810:Mice, Inbred C57BL D019009:Proto-Oncogene Proteins c-kit D034622:RNA Interference D034741:RNA, Small Interfering D013234:Stem Cells
Differentiation Self-renewal Anaphase-promoting complex Cdh1 Hematopoiesis Ubiquitin–proteasome system (UPS)