Estrogen-induced gene expression in bone marrow c-kit+ stem cells and stromal cells: identification of specific biological processes involved in the functional organization of the stem cell niche.

ABSTRACT

The recent interest in the role of bone marrow (BM)-derived endothelial progenitor cells (EPCs) and the benefits of estrogen on cardiovascular health brought us to evaluate if estrogen could affect cardiac repair more broadly by regulating biological processes involved in the functional organization of the BM stem cell (SC) niche. To assess such possibility, we evaluated gene expression profiles of BM c-kit+ SCs and CD44+ stromal cells (StroCs) after exposure to a physiological concentration of 17beta-estradiol (17betaE). Data analysis showed that 17betaE altered the expression (>1.5 fold) of 509 and 682 gene probes in c-kit+ SCs and CD44+ StroCs, respectively. Among them, 199 genes in c-kit+ SCs and 283 in CD44+ StroCs were associated to biological process categories of the Gene Ontology classification. Within processes highly regulated by 17betaE, we identified key factors involved in adhesion, migration, proteolysis, and signaling by which 17betaE influences physiological regulation of the functional organization of the SC niche. Together, our results demonstrate that estrogen benefits on cardiovascular health could involve other BM-derived cells than EPCs and that this capacity of estrogen to influence the physiology of the BM SC niche deserves to be investigated clinically.