Age- and Pregnancy-Associated DNA Methylation Changes in Mammary Epithelial Cells

作者：Huh Sung Jin; Clement Kendell; Jee David; Merlini Alessandra; Choudhury Sibgat; Maruyama Reo; Yoo Ronnie; Chytil Anna; Boyle Patrick; Ran Fei Ann; Moses Harold L; Barcellos Hoff Mary Helen; Jackson Gru**y Laurie; Meissner Alexander^*; Polyak Kornelia

来源：Stem Cell Reports, 2015, 4(2): 297-311.

DOI：10.1016/j.stemcr.2014.12.009

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 TGF beta 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.

• 出版日期2015-2-10