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

Ying Liang, Michael Jansen, Bruce Aronow, Hartmut Geiger, Gary Van Zant

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageEnglish
Pages (from-to)178-188
Number of pages11
JournalNature Genetics
Volume39
Issue number2
DOIs
StatePublished - Feb 2007

Bibliographical note

Funding Information:
We acknowledge the flow cytometric expertise of B. Grimes, the technical assistance of C. Swiderski and the editorial assistance of P. Thomason. This work was supported by the US National Institutes of Health (grants AG020917, AG024950 and AG022859).

ASJC Scopus subject areas

  • Genetics

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