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

被引：47

作者：

Huh, Sung Jin ^{[1
,2
,3
]}

Clement, Kendell ^{[4
,5
,6
,7
]}

Jee, David ^{[1
,2
,3
]}

Merlini, Alessandra ^{[1
,8
]}

Choudhury, Sibgat ^{[1
,2
,3
]}

Maruyama, Reo ^{[1
,2
,3
]}

Yoo, Ronnie ^{[9
,10
]}

Chytil, Anna ^{[11
,12
]}

Boyle, Patrick ^{[4
]}

Ran, Fei Ann ^{[9
,10
]}

Moses, Harold L. ^{[11
,12
]}

Barcellos-Hoff, Mary Helen ^{[13
,14
]}

Jackson-Grusby, Laurie ^{[6
,9
,10
]}

Meissner, Alexander ^{[4
,5
,6
]}

Polyak, Kornelia ^{[1
,2
,3
,4
,6
,9
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA

[4] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[5] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[6] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[7] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[8] Univ Pavia, Dept Mol Med, Unit Immunol & Gen Pathol, I-27100 Pavia, Italy

[9] Harvard Univ, Program Biol & Biomed Sci, Sch Med, Boston, MA 02115 USA

[10] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA

[11] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA

[12] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

[13] NYU, Sch Med, Dept Radiat Oncol, New York, NY 10016 USA

[14] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

来源：

STEM CELL REPORTS | 2015年 / 4卷 / 02期

关键词：

STEM-CELL; GLAND MORPHOGENESIS; CANCER; ACTIVATION; DIFFERENTIATION; PROLIFERATION; POPULATION; LANDSCAPE; GENE; SLUG;

D O I：

10.1016/j.stemcr.2014.12.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：297 / 311

页数：15

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