c-Kit expression and stem cell factor-induced hematopoietic cell proliferation are up-regulated in aged B6D2F1 mice.
Expression of c-Kit (CD117) and stem cell factor/c-Kit-mediated cell proliferation were tested in vitro in young and old B6D2F1 mice to study the role of c-Kit signaling in hematopoietic stem cell (HSC) senescence. Increasing age is associated with a significant increase in bone marrow (BM) cells without affecting mature blood cells. The number of c-Kit-expressing BM cells increased significantly in old mice when compared to young controls, to 201% in total BM cells, 261% in Lin(-) cells, 517% in Lin(-)CD34(+)Sca1(+) progenitor cells, and 1272% in Lin(-)CD34(-)Sca1(+) HSCs. Sorted Lin(-)Sca1(+)CD117(+) BM cells from an old mouse expanded 5-fold when cultured in vitro for 72 hours with stem cell factor at 25 ng/ml, which was significantly higher than a 2.5-fold expansion of the same cells from a young donor. HSCs and progenitor cells from B6D2F1 mice maintain extremely high proliferative potentials and do not reach proliferative arrest at old age during a normal life span.
Smith
Aleah L
AL
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA.
Ellison
Felicia M
FM
McCoy
J Philip
JP
Chen
Jichun
J
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000145:classification / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation; D002469:Cell Separation; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000494:pharmacology*; D015854:Up-Regulation
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit