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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3342-3348.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-09-3202.


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HEMATOPOIESIS

SCL is required for normal function of short-term repopulating hematopoietic stem cells

David J. Curtis, Mark A. Hall, Leonie J. Van Stekelenburg, Lorraine Robb, Stephen M. Jane, and C. Glenn Begley

From the Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, Victoria, Australia; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; the Centre for Child Health Research and Western Australian Institute of Medical Research (WAIMR), The Institute for Child Health Research, Melbourne, Victoria, Australia.

The stem cell leukemia (SCL) gene is essential for the development of hematopoietic stem cells in the embryo. Here, we used a conditional gene targeting approach to examine the function of SCL in adult hematopoietic stem cells (HSCs). Flow cytometry of bone marrow from SCL-deleted mice demonstrated a 4-fold increase in number of Linneg c-kit+ Sca-1+ cells. Despite this increase in the number of phenotypic HSCs, competitive repopulation assays demonstrated a severe multilineage defect in repopulation capacity by SCL-deleted bone marrow cells. SCL-heterozygous cells also showed a mild repopulation defect, thus suggesting haploinsufficiency of SCL. The transplantation defect of SCL-deleted cells was observed within 4 weeks of transplantation, indicating a defect in a multipotent progenitor or short-term repopulating HSCs. Although the defect persisted in secondary transplants, it remained relatively stable, suggesting that SCL was not required for self-renewal of the HSCs. Generation of SCL-deleted cells within SCL-wild-type mice rescued the early repopulating defect. Together, our results suggest that SCL is required for the normal function of short-term repopulating HSCs. (Blood. 2004;103:3342-3348)


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