title: Quantitative trait gene Slit2 positively regulates murine hematopoietic stem cell numbers.
abstract: Hematopoietic stem cells (HSC) demonstrate natural variation in number and function. The genetic factors responsible for the variations (or quantitative traits) are largely unknown. We previously identified a gene whose differential expression underlies the natural variation of HSC numbers in C57BL/6 (B6) and DBA/2 (D2) mice. We now report the finding of another gene, Slit2, on chromosome 5 that also accounts for variation in HSC number. In reciprocal chromosome 5 congenic mice, introgressed D2 alleles increased HSC numbers, whereas B6 alleles had the opposite effect. Using gene array and quantitative polymerase chain reaction, we identified Slit2 as a quantitative trait gene whose expression was positively correlated with the number of HSCs. Ectopic expression of Slit2 not only increased the number of the long-term colony forming HSCs, but also enhanced their repopulation capacity upon transplantation. Therefore, Slit2 is a novel quantitative trait gene and a positive regulator of the number and function of murine HSCs. This finding suggests that Slit2 may be a potential therapeutic target for the effective in vitro and in vivo expansion of HSCs without compromising normal hematopoiesis.
authors: Division of Mathematics and Natural Sciences, Somerset Community College, Laurel Campus, London, KY, USA.
authors: Amanda
authors: A
authors: Waterstrat
authors: Department of Physiology, University of Kentucky, Lexington, KY, USA.
authors: Kyle
authors: K
authors: Rector
authors: Division of Experimental Hematology and Cancer Biology, Children's Hospital Medical Center, Cincinnati, OH, USA.|Department of Dermatology and Allergic Disease, University of Ulm, Ulm, Germany.
authors: Hartmut
authors: H
authors: Geiger
authors: Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, USA.
authors: Ying
authors: Y
authors: Liang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D040641:Quantitative Trait Loci; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000098552:Slit Homolog 2 Protein