The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice

• Published in: Nature genetics Vol. 39; no. 2; pp. 178 - 188
• Main Authors: Van Zant, Gary, Liang, Ying, Jansen, Michael, Aronow, Bruce, Geiger, Hartmut
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.02.2007
• Subjects: Animals; Antigens - genetics; Antigens - metabolism; Apoptosis; Biological and medical sciences; Cell Count; Cell Proliferation; Chromosome Mapping; Chromosomes; DNA binding proteins; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene mapping; Genes; Genes, Regulator; Genetic aspects; Genetic Linkage; Genetic polymorphisms; Genetics of eukaryotes. Biological and molecular evolution; Hematopoietic stem cells; Hematopoietic Stem Cells - physiology; House mouse; Mice; Mice, Congenic; Mice, Inbred C57BL; Mice, Inbred DBA; Polymorphism, Single Nucleotide; Population number; Quantitative genetics; Quantitative Trait Loci; Rodents; Stem cells; Transcription (Genetics); Transduction, Genetic; Vertebrata; Mammalia; Gene; Cell population; Mouse; Quantitative character; Stem cell; Rodentia; Hematopoietic cell
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1938

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.