Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [mRRBS]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE54149 | GEO | 2015/01/22
SECONDARY ACCESSION(S): PRJNA235306
REPOSITORIES: GEO
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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: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. 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. 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:The mammary gland develops mainly postnatally, when during pregnancy the epithelium grows out into the mammary fat pad and forms a network of epithelial ducts. During pregnancy, these ducts branch and bud to form alveoli. These alveoli produce the milk during lactation. After 7 days of lactation, involution was induced by force weaning the pups. The newly formed epithelium undergoes apoptosis and is removed from the tissue by neighbouring epithelial cells. Tissue remodelling leads to a morphology resembling a gland of a pre-pregnant mouse. Microarray analysis was used to measure mRNA expression of genes during puberty, pregnancy, lactation and involution in a Balb/c mouse strain. Keywords: developmental time course
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Project description:The mammary gland develops mainly postnatally, when during pregnancy the epithelium grows out into the mammary fat pad and forms a network of epithelial ducts. During pregnancy, these ducts branch and bud to form alveoli. These alveoli produce the milk during lactation. After 7 days of lactation, involution was induced by force weaning the pups. The newly formed epithelium undergoes apoptosis and is removed from the tissue by neighbouring epithelial cells. Tissue remodelling leads to a morphology resembling a gland of a pre-pregnant mouse. Microarray analysis was used to measure mRNA expression of genes during puberty, pregnancy, lactation and involution in a Balb/c mouse strain. Experiment Overall Design: Total RNA was extracted from the 4th (inguinal) gland after removal of the lymph node. Individual samples represent RNA from one gland of one mouse. Samples were taken in triplicate (i.e. three mice per triplicate) for 18 time points of development.
2008-10-21 | E-GEOD-12247 | biostudies-arrayexpress
Project description:The mammary gland is a dynamic tissue that mainly develops postnatally under the influence of fluctuating hormone levels. This dataset contains bulk RNAseq data of different mouse mammary gland cell populations (basal, luminal and stromal) that were isolated either during puberty or at different stages of the adult virgin estrous cycle. These data are of interest to researchers in the mammary gland and breast cancer biology field as they allow studies on spatiotemporal, lineage specific changes in gene expression.
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Project description:During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages. Using RNA-seq, we show that basal cells are extraordinarily transcriptionally dynamic throughout pregnancy when compared to luminal cells. We identified gene expression changes that define specific basal functions acquired during development that led to the identification of novel markers. Enrichment analysis of gene sets from 24 mouse models for breast cancer pinpoint to a potential new function for insulin-like growth factor 1 (Igf1r) in the basal epithelium during lactogenesis. We establish that β-catenin signaling is activated in basal cells during early pregnancy, and demonstrate that this activity is mediated by lysophosphatidic acid receptor 3 (Lpar3). These findings identify novel pathways active during functional maturation of the adult mammary gland.
2016-10-21 | GSE88984 | GEO
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
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