Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Kendell Clement
PROVIDER: E-GEOD-54150 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project 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.
2015-01-22 | E-GEOD-54148 | biostudies-arrayexpress
Project description:Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Mammary glands were collected from different reproductive stages to purify different epithelium cell types, which were used for RNA extraction and hybridization on Affymetrix microarrays.
2015-01-22 | E-GEOD-54147 | biostudies-arrayexpress
Project description:Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Mammary glands were collected from mice at non-pregnant and pregnant stages for DNA extraction and DNA methylation analysis via mRRBS (multiplexed reduced representation bisulfite sequencing).
2015-01-22 | E-GEOD-54149 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-11-26 | E-GEOD-47377 | biostudies-arrayexpress
Project description:RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss. Thoracic and inguinal mammary glands from 3 MMTV-Cre;Runx1L/L;R26Y and 3 MMTV-Cre;Runx1+/+;R26Y adult virgin females were dissected out, minced and digested to single cell suspension. Runx1L is the floxed conditional knockout allele of Runx1. R26Y is a conditional YFP reporter that would be turned on upon Cre-mediated recombination. FACSaria machine was used to sort out the YFP-marked luminal epithelial cell population of each of these 6 mice. Total RNA was isolated with Qiagen RNeasy kit and subsequently amplified by Nugen V2 and applied to Affymetrix mouse genome 430 2.0 arrays.
2014-11-26 | E-GEOD-47375 | biostudies-arrayexpress
Project description:The purpose of this microarray experiment was to obtain reference gene expression patterns of a number of epithelial cell populations [mammary stem cells (MASC), luminal progenitors (LP), alveolar luminal stem/progenitor cells (WC virgin-these are mammary epithelial cells genetically marked by Wap-Cre in virgin females), mature luminal cells (ML, mainly represent ductal luminal cells in virgin females), and alveolar luminal cells (WC preg M-bM-^@M-^S these are alveolar cells genetically marked by Wap-Cre during mid-gestation)] present in the mammary gland of wildtype adult mice on a C57BL6 genetic background. For the isolation of RNA from mammary stem cells (MASC, Lin-CD24+CD29hi), luminal progenitors (LP, Lin-CD24hiCD29+CD61+), and mature luminal cells (ML, lin-CD24hiCD29+CD61-), the thoracic and inguinal mammary glands from 3 adult virgin female mice were harvested, minced and digested into a single cell suspension. Form each of these 3 single cell suspensions, the above populations were sorted by FACS. For alveolar luminal stem/progenitor cells and alveolar luminal cells, Lin-YFP+ mammary epithelial cells were isolated from virgin or midgestation mice genetically marked by Wap-Cre;R26Y. R26Y is a conditional YFP reporter that would be turned on upon Cre-mediated recombination.
2014-11-26 | E-GEOD-47376 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-19 | E-GEOD-47493 | biostudies-arrayexpress
Project description:MaSC, Luminal progenitor enriched subpopulations were isolated from virgin and pregnant mice based on using both surface marker or internal reporter transgene (GFP) expression. (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035), and the transcirptome profiles were determined and compared. Two MaSC differential methods: CD24/CD29 & GFP reporter; two physiolgical condition: virgin vs pregnant; the combination of ((P4, GFPhi) vs (P5, P6, GFPlo)) x (vg vs pg)
2014-08-19 | E-GEOD-47419 | biostudies-arrayexpress
Project description:We have compared an involution timecourse for wild type and E2F3 heterozygous mice on the Operon 3.0 platform. Three mice were taken for each genotype at each timepoint (Involution day 0, 1, 2, 3 and 4) and RNA was prepared from the mammary glands. The RNA from each mouse was pooled and run as an individual sample. Keywords: Mouse Mammary Gland RNA 5 timepoints, 2 genotypes, 3 replicates per timepoint.
2008-07-11 | E-GEOD-11066 | biostudies-arrayexpress
Project description:Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive “metastatic niches” within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth. Three chips were done per organ (liver/lung) and per condition (virgin/pregnant), with equal amounts of RNA from two mice pooled for one chip.
2011-03-19 | E-GEOD-18907 | biostudies-arrayexpress