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Accession IconGSE54148

Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [inhibitor study]

Organism Icon Mus musculus
Sample Icon 15 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

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Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. To explore the role of DNA methylation in luminal cell differentiation and pregnancy-induced changes, we determined the genome-wide DNA methylation and gene expression profiles of mammary epithelial stem, luminal progenitor, and mature luminal cells at different reproductive stages. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell type and reproductive stage-specific changes in molecular signatures. We also identified p27 and TGF signaling as key regulators of luminal progenitor cell proliferation based on their expression patterns and by the use of explant cultures. Our results suggest relatively minor changes in DNA methylation during luminal cell differentiation as compared to the significant effects of pregnancy on mammary epithelial stem cells.
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