Genes that Control the Size of the Stem Cell Compartment

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In collaboration with the Riblet group we were the first to describe a marked difference in the number of HSC in the bone marrow of different strains of mice [J.Exp Med.1996;183: 1141]. C57BL/6 (B6) mice, the most common strain of mice used for HSC research contained the lowest number of HSC. In contrast, DBA/2 (D2) mice show 10-fold higher frequencies of HSC than B6. Quantitative Trait Linkage analysis of the level of stem cells in BXD RI strains indicated 1) multigenic control of stem cell frequency, and 2) two loci, named Scfr-1 and Scfr-2, that have major quantitative effects are located on chromosome 1. Thus, the regulation of the size of the stem cell pool has a strong genetic component. Analysis of blastocyst aggregation chimeras together with mathematical modeling (OMM) showed that the effect of the Scfr genes is mostly stem cell intrinsic. Preliminary data indicate that the different Scfr alleles predict the ability to mobilize stem cells to the periphery after cytokine stimulation. This suggests that the Scfr genes could be a much needed predictor of mobilization potential. Extensive genetic analysis of the Scfr loci demonstrated epigenetic regulation of the genes. This precluded the identification of the Scfr genes by classical genetic approaches. More recently, several candidate genes were identified by screening for differential expression in the Lin- HSC compartment of the strains B6 and D2. We are currently working to determine whether these genes control the size of the HSC compartment and if so, by which mechanisms.


Hematopoietic Stem Cells

Lineage-biased Stem Cells Detected in Clonal Analysis

Aging of Hematopoietic Stem Cells

Markers for Hematopoietic Stem Cells

Genes that Control the Size of the Stem Cell Compartment