Impaired adult myeloid progenitor CMP and GMP cell function in conditional c-myb-knockout mice.
The differentiation of myeloid progenitors to mature, terminally differentiated cells is a highly regulated process. Here, we showed that conditional disruption of the c-myb proto-oncogene in adult mice resulted in dramatic reductions in CMP, GMP and MEP myeloid progenitors, leading to a reduction of neutrophils, basophils, monocytes and platelets in peripheral blood. In addition, c-myb plays a critical role at multiple stages of myeloid development, from multipotent CMP and bipotent GMP to unipotent CFU-G and CFU-M progenitor cells. c-myb controls the differentiation of these cells and is required for the proper commitment, maturation and normal differentiation of CMPs and GMPs. Specifically, c-myb regulates the precise commitment to the megakaryocytic and granulo-monocytic pathways and governs the granulocytic-monocytic lineage choice. c-myb is also required for the commitment along the granulocytic pathway for early myeloid progenitor cells and for the maturation of committed precursor cells along this pathway. On the other hand, disruption of the c-myb gene favors the commitment to the monocytic lineage, although monocytic development was abnormal with cells appearing more mature with atypical CD41 surface markers. These results demonstrate that c-myb plays a pivotal role in the regulation of multiple stages in adult myelogenesis.
Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA. ykl2104@columbia.edu
Yen K
YK
Lieu
E Premkumar
EP
Reddy
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D055015:Megakaryocyte-Erythroid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*
D020598:Proto-Oncogene Proteins c-myb; C045073:Cre recombinase; D019426:Integrases