Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.

Stem Cell Reports
Authors
Keywords
Abstract

Postnatal mammary gland development and differentiation occur during puberty and pregnancy. To explore the role of DNA methylation in these processes, we determined the genome-wide DNA methylation and gene expression profiles of CD24(+)CD61(+)CD29(hi), CD24(+)CD61(+)CD29(lo), and CD24(+)CD61(-)CD29(lo) cell populations that were previously associated with distinct biological properties at different ages and reproductive stages. We found that pregnancy had the most significant effects on CD24(+)CD61(+)CD29(hi) and CD24(+)CD61(+)CD29(lo) cells, inducing distinct epigenetic states that were maintained through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell-type- and reproductive-stage-specific changes. We identified p27 and TGFβ signaling as key regulators of CD24(+)CD61(+)CD29(lo) cell proliferation, based on their expression patterns and results from mammary gland explant cultures. Our results suggest that relatively minor changes in DNA methylation occur during luminal differentiation compared with the effects of pregnancy on CD24(+)CD61(+)CD29(hi) and CD24(+)CD61(+)CD29(lo) cells.

Year of Publication
2015
Journal
Stem Cell Reports
Volume
4
Issue
2
Pages
297-311
Date Published
2015 Feb 10
ISSN
2213-6711
URL
DOI
10.1016/j.stemcr.2014.12.009
PubMed ID
25619437
PubMed Central ID
PMC4325231
Links
Grant list
F32 CA156991 / CA / NCI NIH HHS / United States
P01 CA080111 / CA / NCI NIH HHS / United States