Genes changed in LSK cells (bone marrow) as a function of a QTL for the size of hematopoietic stem cell (HSC) population: comparison of reciprocal congenic strains D.B. Chr3 (DB), B.D. Chr3 (BD) and the parental strains B6 and D2.
Full description or abstract
We mapped quantitative trait loci that accounted for the variation in hematopoietic stem cell (HSC) numbers between young adult C57BL/6 (B6) and DBA/2 (D2) mice. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles increased HSC numbers owing to enhanced proliferation and self-renewal and reduced apoptosis, whereas B6 alleles had the opposite effects. Using oligonucleotide arrays, real-time PCR and protein blots, we identified latexin (Lxn), a gene whose differential transcription and expression was associated with the allelic differences. Expression was inversely correlated with the number of HSCs; therefore, ectopic expression of Lxn using a retroviral vector decreased stem cell population size. We identified clusters of SNPs upstream of the Lxn transcriptional start site, at least two of which are associated with potential binding sites for transcription factors regulating stem cells. Thus, promoter polymorphisms between the B6 and D2 alleles may affect Lxn gene expression and consequently influence the population size of hematopoietic stem cells.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
Source publication
Pubmed 17220891 Authors: Liang Y,Jansen M,Aronow B,Geiger H,Van Zant G
