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

First Author  Curtis DJ Year  2004
Journal  Blood Volume  103
Issue  9 Pages  3342-8
PubMed ID  14726374 Mgi Jnum  J:90290
Mgi Id  MGI:3042823 Doi  10.1182/blood-2003-09-3202
Citation  Curtis DJ, et al. (2004) SCL is required for normal function of short-term repopulating hematopoietic stem cells. Blood 103(9):3342-8
abstractText  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 Lin(neg) 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.
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