Age-associated characteristics of murine hematopoietic stem cells.
Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34(-/low)c-Kit(+)Sca-1(+) lineage marker-negative (CD34(-)KSL) cells from the bone marrow of C57BL/6 mice. A population of CD34(-)KSL cells gradually expanded as age increased. Regardless of age, these cells formed in vitro colonies with stem cell factor and interleukin (IL)-3 but not with IL-3 alone. They did not form day 12 colony-forming unit (CFU)-S, indicating that they are primitive cells with myeloid differentiation potential. An in vivo limiting dilution assay revealed that numbers of multilineage repopulating cells increased twofold from 2 to 18 mo of age within a population of CD34(-)KSL cells as well as among unseparated bone marrow cells. In addition, we detected another compartment of repopulating cells, which differed from HSCs, among CD34(-)KSL cells of 18-mo-old mice. These repopulating cells showed less differentiation potential toward lymphoid cells but retained self-renewal potential, as suggested by secondary transplantation. We propose that HSCs gradually accumulate with age, accompanied by cells with less lymphoid differentiation potential, as a result of repeated self-renewal of HSCs.
Sudo
K
K
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tsukuba, Japan.
Ema
H
H
Morita
Y
Y
Nakauchi
H
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit