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E-GEOD-54148 - Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [inhibitor study]

Status
Released on 22 January 2015, last updated on 4 February 2015
Organism
Mus musculus
Samples (15)
Array (1)
Protocols (7)
Description
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. 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.
Experiment type
transcription profiling by array 
Contacts
Kendell Clement <geo@ncbi.nlm.nih.gov>, Alexander Meissner, Kornelia Polyak, Patrick Boyle, Sung J Huh
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-54148.idf.txt
Sample and data relationshipE-GEOD-54148.sdrf.txt
Raw data (1)E-GEOD-54148.raw.1.zip
Processed data (1)E-GEOD-54148.processed.1.zip
Array designA-AFFY-36.adf.txt
Links