期刊
STEM CELL REPORTS
卷 4, 期 2, 页码 297-311出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2014.12.009
关键词
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资金
- National Cancer Institute [F32 CA156991, P01 CA080111]
- Giovanni Armenise-Harvard Foundation Summer Fellowship Program
- Susan G. Komen Foundation
- Terri Brodeur Foundation
- New York Stem Cell Foundation
- U.S. Army Congressionally Directed Research [W81XWH-07-1-0294]
- Grants-in-Aid for Scientific Research [25640079] Funding Source: KAKEN
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.
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