Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells
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ABSTRACT:
PROVIDER: PRJNA235304 | ENA |
REPOSITORIES: ENA
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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.
2015-01-22 | GSE54148 | GEO
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 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: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.
2015-01-22 | GSE54149 | GEO
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.
2015-01-22 | GSE54147 | GEO
Project description:R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic functions in development and stem cell growth. Rspo1 knock-out mice are sex-reversed, but some remain sub-fertile, so, they are unable to nurse their pups. A lack of Rspo1 expression in mammary epithelial cells results in an absence of duct side-branching development and defective alveolar formation. In this study we propose to characterize the molecular functions involved to mammary gland phenotype due to Rspo1 knock out. By transcriptional profiling, we have identified gene misregulated in mammary gland of Rspo1 knock-out mice during pregnancy. A stronger expression of genes characterising mesenchymal tissue was observed in the absence of alterations to the structure of mammary epithelial tissue. Mammary epithelial cell characterization, by immunohistochemistry approach, revealed a persistence of virgin markers which sign a delay in their differentiation. Moreover serial transplantation experiments show that Rspo1 is associated with a regenerative potential of mammary epithelial cell control. Our data have also highlighted that in mammary gland during pregnancy the expression of Rspo1’s partners, Lgr4 and RNF43, are negatively regulated and Tgf-β signaling is modified in the absence of Rspo1. Taken together, our results show an abrupt halt in mammary development at mid-pregnancy due to loss of further differentiated function.
2017-02-09 | GSE81244 | GEO
Project description:The mouse mammary gland undergoes severe morphological changes during each pregnancy cycle. These are controlled by epithelial as well as stromal factors, including fibroblasts. This project aimed to identify factors that are expressed in mammary fibroblasts during early pregnancy (day3) when the first morphological changes become microscopically visible.
2021-09-28 | GSE167438 | GEO
Project description:Pregnancy is the major modulator of mammary gland activity. It induces a tremendous expansion of the mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the mammary gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here we verify that the mouse mammary gland responds more robustly to a second pregnancy, indicating that the gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated mammary cell types revealed substantial and long lasting alterations. The majority of these alterations affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote mammary gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.
2015-05-15 | GSE67386 | GEO
Project description:The aim of this study was to identify transcriptional changes in hormone receptor positive (HR+) cells during the dynamic morphogenesis in mammary epithelium during early pregnancy. HR+ cells translate the systemic hormonal signals that indicate pregnancy into local instructions for the generation of alveoli (milk-producing units). We previously found that IGF-2 is produced by HR+ cells, but this is only detectable in early pregnancy and not in virgin animals. This data set was generated to charachterize what other genes become expressed in HR+ cells specifically during a time of active proliferation and cellular communication. The gene expression profile at 3 days of pregnancy shows a marked upregulation of genes involved in cell division. By the 7th day of pregnancy the HR+ cells induce expression of several secreted molecules. Taken together with EdU incorporation analysis, we find that HR+ cells first undergo an expansion phase and subsequently express paracrine stimulators of alveolar and basal mammary epithelial cells during early pregnancy.
2014-12-02 | GSE63720 | GEO