Work

The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice

Year: 2015

Type: article

Abstract: Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS) strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC) frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx). Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx-/- mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system.

Source: Stem Cell Reports

DOI: 10.1016/j.stemcr.2015.05.008

Authors: Xiaoying Zhou, Amanda L. Crow, Jaana Hartiala, Tassja J. Spindler, Anatole Ghazalpour, Lora W. Barsky, Brian J. Bennett, Brian W. Parks, Eleazar Eskin, Rajan Jain, Jonathan A. Epstein, Aldons J. Lusis, Gregor B. Adams, Hooman Allayee

Institutions: University of Southern California, Broad Center, University of California, Los Angeles, University of North Carolina at Chapel Hill, University of Pennsylvania

Language: English

Topic: Hematopoietic Stem Cell Transplantation

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,190

Funders: California Institute for Regenerative Medicine, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences

Awards: Systems Genetics Analysis of Gene-by-Environment Interactions in Obesity, G1353353046, G1480891745, Genetic and Environmental Determinants of Asthma Endophenotypes, Analysis of a Novel Homeobox gene in CV Development, Lipid and Lipoprotein Metabolism in Atherosclerosis, Southern California Clinical and Translational Science Institute, Correcting for Population Structure in Gene-by-Environment Interaction Studies, High-Resolution Systems Genetic Studies of Atherosclerotic Lesion Composition, CIRM Stem Cell Biology Training Program, G491034554, G591327864, INTEGRATIVE GENETIC APPROACHES TO GENE-AIR POLLUTION INTERACTIONS IN ASTHMA, Investigating the role of Hopx in cardiac progenitor proliferation, G9000143528, Environmental Exposures, Host Factors and Human Disease

OpenAlex ID: W1923650300

FWCI: 2.35

Cites: 54

Cited by: 28

Related to: 10