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 Blood, 15 October 2006, Vol. 108, No. 8, pp. 2850-2856.
Prepublished online as a Blood First Edition Paper on June 27, 2006; DOI 10.1182/blood-2006-03-010207.

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STEM CELLS IN HEMATOLOGY

Non-side-population hematopoietic stem cells in mouse bone marrow

Yohei Morita, Hideo Ema, Satoshi Yamazaki, and Hiromitsu Nakauchi

From the Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo; and ReproCell, Tokyo, Japan.

Most hematopoietic stem cells (HSCs) are assumed to reside in the so-called side population (SP) in adult mouse bone marrow (BM). We report the coexistence of non-SP HSCs that do not significantly differ from SP HSCs in numbers, capacities, and cell-cycle states. When stained with Hoechst 33342 dye, the CD34-/low c-Kit+Sca-1+lineage marker- (CD34-KSL) cell population, highly enriched in mouse HSCs, was almost equally divided into the SP and the main population (MP) that represents non-SP cells. Competitive repopulation assays with single or 30 SP- or MP-CD34-KSL cells found similar degrees of repopulating activity and frequencies of repopulating cells for these populations. Secondary transplantation detected self-renewal capacity in both populations. SP analysis of BM cells from primary recipient mice suggested that the SP and MP phenotypes are interconvertible. Cell-cycle analyses revealed that CD34-KSL cells were in a quiescent state and showed uniform cell-cycle kinetics, regardless of whether they were in the SP or MP. Bcrp-1 expression was similarly detected in SP- and MP-CD34-KSL cells, suggesting that the SP phenotype is regulated not only by Bcrp-1, but also by other factors. The SP phenotype does not specify all HSCs; its identity with stem cell function thus is unlikely.


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Repopulating Activity of Ex Vivo-Expanded Murine Hematopoietic Stem Cells Resides in the CD48-c-Kit+Sca-1+Lineage Marker- Cell Population
Stem Cells, March 1, 2008; 26(3): 646 - 655.
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