Quantitative trait gene Slit2 positively regulates murine hematopoietic stem cell numbers

Amanda Waterstrat, Kyle Rector, Hartmut Geiger, Ying Liang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Article number31412
JournalScientific Reports
StatePublished - Sep 8 2016

Bibliographical note

Funding Information:
National Institutes of Health, through grant number KL2TR000116

ASJC Scopus subject areas

  • General


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