Age-associated Characteristics of Murine Hematopoietic Stem Cells

doi:10.1084/jem.192.9.1273

Published online 30 October 2000.

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© The Rockefeller University Press, 0022-1007/2000/11/1273/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 9, November 6, 2000 1273-1280

Original Article

Age-associated Characteristics of Murine Hematopoietic Stem Cells

Kazuhiro Sudo^a, Hideo Ema^a, Yohei Morita^a, and Hiromitsu Nakauchi^a
^a 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 305-8575, Japan

Correspondence to: Hiromitsu Nakauchi, Dept. of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Tel:81-298-53-6964 Fax:81-298-53-6966

Little is known of age-associated functional changes in hematopoieticstem cells (HSCs). We studied aging HSCs at the clonal levelby isolating CD34^-/lowc-Kit⁺Sca-1⁺ lineage marker–negative(CD34^-KSL) cells from the bone marrow of C57BL/6 mice. A populationof CD34^-KSL cells gradually expanded as age increased. Regardlessof age, these cells formed in vitro colonies with stem cellfactor and interleukin (IL)-3 but not with IL-3 alone. Theydid not form day 12 colony-forming unit (CFU)-S, indicatingthat they are primitive cells with myeloid differentiation potential.An in vivo limiting dilution assay revealed that numbers ofmultilineage repopulating cells increased twofold from 2 to18 mo of age within a population of CD34^-KSL cells as well asamong unseparated bone marrow cells. In addition, we detectedanother compartment of repopulating cells, which differed fromHSCs, among CD34^-KSL cells of 18-mo-old mice. These repopulatingcells showed less differentiation potential toward lymphoidcells but retained self-renewal potential, as suggested by secondarytransplantation. We propose that HSCs gradually accumulate withage, accompanied by cells with less lymphoid differentiationpotential, as a result of repeated self-renewal of HSCs.

Key Words: mouse, bone marrow transplantation, hematopoiesis, self-renewal,differentiation

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