SCL is required for normal function of short-term repopulating hematopoietic stem cells.
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.
Curtis
David J
DJ
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. dcurtis@wehi.edu.au
Hall
Mark A
MA
Van Stekelenburg
Leonie J
LJ
Robb
Lorraine
L
Jane
Stephen M
SM
Begley
C Glenn
CG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology*; D005434:Flow Cytometry; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse