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Status |
Public on Jan 22, 2015 |
Title |
Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [inhibitor study] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. To explore the role of DNA methylation in luminal cell differentiation and pregnancy-induced changes, we determined the genome-wide DNA methylation and gene expression profiles of mammary epithelial stem, luminal progenitor, and mature luminal cells at different reproductive stages. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell type and reproductive stage-specific changes in molecular signatures. We also identified p27 and TGFβ signaling as key regulators of luminal progenitor cell proliferation based on their expression patterns and by the use of explant cultures. Our results suggest relatively minor changes in DNA methylation during luminal cell differentiation as compared to the significant effects of pregnancy on mammary epithelial stem cells.
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Overall design |
Mammary glands were collected from mice treated with DNA methylation inhibitor 5-azacytidine (AzaC) and histone deacetylase inhibitor valproic acid (VPA) at non-pregnant and pregnant stages for RNA extraction and hybridization on Affymetrix microarrays.
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Contributor(s) |
Huh SJ, Clement K, Boyle P, Meissner A, Polyak K |
Citation(s) |
25619437 |
Submission date |
Jan 16, 2014 |
Last update date |
May 04, 2018 |
Contact name |
Kendell Clement |
Organization name |
Harvard University
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Lab |
Meissner Lab
|
Street address |
7 Divinity Ave.
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02138 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (15)
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GSM1308891 |
Mammary epithelial cells from pregnant mice PBS control replicate 1 |
GSM1308892 |
Mammary epithelial cells from pregnant mice PBS control replicate 2 |
GSM1308893 |
Mammary epithelial cells from Aza treated pregnant mice replicate 1 |
GSM1308894 |
Mammary epithelial cells from Aza treated pregnant mice replicate 2 |
GSM1308895 |
Mammary epithelial cells from Aza treated pregnant mice replicate 3 |
GSM1308896 |
Mammary epithelial cells from VPA treated pregnant mice replicate 1 |
GSM1308897 |
Mammary epithelial cells from VPA treated pregnant mice replicate 2 |
GSM1308898 |
Mammary epithelial cells from VPA treated pregnant mice replicate 3 |
GSM1308899 |
Mammary epithelial cells from virgin mice PBS control replicate 1 |
GSM1308900 |
Mammary epithelial cells from virgin mice PBS control replicate 2 |
GSM1308901 |
Mammary epithelial cells from Aza treated virgin mice replicate 1 |
GSM1308902 |
Mammary epithelial cells from Aza treated virgin mice replicate 2 |
GSM1308903 |
Mammary epithelial cells from Aza treated virgin mice replicate 3 |
GSM1308904 |
Mammary epithelial cells from VPA treated virgin mice replicate 1 |
GSM1308905 |
Mammary epithelial cells from VPA treated virgin mice replicate 2 |
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This SubSeries is part of SuperSeries: |
GSE54150 |
Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells |
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Relations |
BioProject |
PRJNA235305 |