Mus musculus
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ABSTRACT:
PROVIDER: PRJNA235305 | ENA |
REPOSITORIES: ENA
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Project description:Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells
| PRJNA235304 | ENA
Project description:Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [mRRBS]
| PRJNA235306 | ENA
Project description:Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [reproductive stages]
| PRJNA235307 | ENA
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. 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: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 Mammary gland undergoes complicated epithelial remodeling to form lobuloalveoli during pregnancy, in which basal epithelial cells remarkably increase to form a basket-like architecture. However, it remains largely unknown how dormant mammary basal stem/progenitor cells involve in lobuloalveolar development. Here, we show that Nfatc1 expression marks a rare population of mammary epithelial cells with the majority being basal epithelial cells. Nfatc1 reporter-marked basal epithelial cells are relatively dormant mammary stem/progenitor cells. Although Nfatc1 reporter-marked basal epithelial cells show limited contribution to the homeostasis of mammary epithelium, they divide rapidly during pregnancy and contribute to lobuloalveolar development. Furthermore, Nfatc1 reporter-marked basal epithelial cells are preferentially used for multiple pregnancies. Using single-cell RNA-seq analysis, we identify multiple functionally distinct clusters within the Nfatc1 reporter-marked cell-derived progeny cells during pregnancy. Taken together, our findings underscore Nfatc1 reporter-marked basal cells as dormant stem/progenitor cells that contribute to mammary lobuloalveolar development during pregnancy.
2022-02-18 | GSE175432 | 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. Mammary gland cells (six distinct cell types) from nulliparous and parous female mice were FACS-sorted using a combination of cell surface markers. Genomic DNA was bisulfite converted and used to obtain genome-wide DNA methylation profiles. The current work focuses on the analysis of the first 12 samples (GSM1646785-96) and uses the other two samples to confirm some properties of the analysis results based on samples 1-12. Consequently, samples GSM1646797, GSM1646798 were analyzed in a much more limited manner compared to the other 12 samples, generating two plots included in the associated manucript.
2015-05-15 | E-GEOD-67386 | biostudies-arrayexpress
Project description:The mammary gland undergoes extensive remodeling between the begin- ning of pregnancy and lactation; this involves cellular processes including cell proliferation, differentiation, and apoptosis, all of which are under the control of numerous regulators. To unravel the role played by miRNA, we describe here 47 new ovine miRNA cloned from mammary gland in early pregnancy displaying strong similari- ties with those already identified in the cow, human, or mouse. A microarray study of miRNA variations in the adult ovine mammary gland during pregnancy and lactation showed that 100 miRNA are regulated according to three principal patterns of expression: a de- crease in early pregnancy, a peak at midpregnancy, or an increase throughout late pregnancy and lactation. One miRNA displaying each pattern (miR-21, miR-205, and miR-200b) was analyzed by qRT- PCR. Variations in expression were confirmed for all three miRNA. Using in situ hybridization, we detected both miR-21 and miR-200 in luminal mammary epithelial cells when expressed, whereas miR-205 was expressed in basal cells during the first half of pregnancy and then in luminal cells during the second half. We therefore conclude that miR-21 is strongly expressed in the luminal cells of the normal mammary gland during early pregnancy when extensive cell prolif- eration occurs. In addition, we show that miR-205 and miR-200 are coexpressed in luminal cells, but only during the second half of pregnancy. These two miRNA may cooperate to maintain epithelial status by repressing an EMT-like program, to achieve and preserve the secretory phenotype of mammary epithelial cells. 5 samples for sheep and 5 samples for mouse
2013-01-04 | E-GEOD-32654 | biostudies-arrayexpress
Project description:Maternal exposures during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. We investigated whether feeding pregnant rats a high fat (HF) or ethinyl-estradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. Here we show that mammary tumorigenesis is higher in daughters and granddaughters of HF rat dams and in daughters, granddaughters and great-granddaughters of EE2 rat dams. Outcross experiments indicate that increased mammary cancer risk is transmitted to HF granddaughters equally through the female or male germlines, but it is only transmitted to EE2 granddaughters through the female germline. The effects of maternal EE2 exposure on offspring's mammary cancer risk are associated with alternations in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and estrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through non-genetic means We examined the whole genome methylation status of both control and EE2-supplemented diet rats in three consecutive generations
2012-09-20 | E-GEOD-40251 | biostudies-arrayexpress