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

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

doi:10.1016/j.stemcr.2014.12.009

Stem Cell Reports (Feb 2015)

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

Sung Jin Huh,
Kendell Clement,
David Jee,
Alessandra Merlini,
Sibgat Choudhury,
Reo Maruyama,
Ronnie Yoo,
Anna Chytil,
Patrick Boyle,
Fei Ann Ran,
Harold L. Moses,
Mary Helen Barcellos-Hoff,
Laurie Jackson-Grusby,
Alexander Meissner,
Kornelia Polyak

Affiliations

Sung Jin Huh: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Kendell Clement: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
David Jee: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Alessandra Merlini: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Sibgat Choudhury: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Reo Maruyama: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Ronnie Yoo: Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA
Anna Chytil: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Patrick Boyle: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Fei Ann Ran: Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA
Harold L. Moses: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Mary Helen Barcellos-Hoff: Departments of Radiation Oncology and Cell Biology, New York University School of Medicine, New York, NY 10016, USA
Laurie Jackson-Grusby: Harvard Stem Cell Institute, Cambridge, MA 02138, USA
Alexander Meissner: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Kornelia Polyak: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA

DOI: https://doi.org/10.1016/j.stemcr.2014.12.009
Journal volume & issue: Vol. 4, no. 2
pp. 297 – 311

Abstract

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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+CD29hi, CD24+CD61+CD29lo, and CD24+CD61−CD29lo 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+CD29hi and CD24+CD61+CD29lo 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+CD29lo 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+CD29hi and CD24+CD61+CD29lo cells.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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