The Journal of Experimental Medicine
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Published online 6 November 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 Sudoa, Hideo Emaa, Yohei Moritaa, and Hiromitsu Nakauchia

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
Dept. of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), 1-1-1 Tennodai, Tsukuba 305-8575, Japan.81-298-53-696681-298-53-6964

Little is known of age-associated functional changes in hematopoietic stem cells (HSCs). We studied aging HSCs at the clonal level by isolating CD34–/lowc-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.

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

Abbreviations used in this paper: HSCs, hematopoietic stem cells; PI, propidium iodide; SCF, stem cell factor.

© 2000 The Rockefeller University Press


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