SCL is required for normal function of short-term repopulating hematopoietic stem cells
- Author(s)
- Curtis, DJ; Hall, MA; Van Stekelenburg, LJ; Robb, L; Jane, SM; Begley, CG;
- Details
- Publication Year 2004-05-01,Volume 103,Issue #9,Page 3342-3348
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- 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. (C) 2004 by The American Society of Hematology.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- TRANSCRIPTION FACTOR SCL; COLONY-FORMING CELLS; C-KIT EXPRESSION; IN-VIVO; COMPETITIVE REPOPULATION; LIMITING DILUTION; PROGENITOR CELLS; MICE LACKING; BONE-MARROW; LEUKEMIA
- Publisher's Version
- https://doi.org/10.1182/blood-2003-09-3202
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-05-01 12:00:00