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, C. Glenn Begley

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64 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3342-3348
Number of pages7
JournalBlood
Volume103
Issue number9
DOIs
Publication statusPublished - 1 May 2004
Externally publishedYes

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