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Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells

ABSTRACT: Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells

PROVIDER: PRJNA235304 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1121240.fastq.gz	Fastqsanger.gz
	SRR1121250.fastq.gz	Fastqsanger.gz
	SRR1121241.fastq.gz	Fastqsanger.gz
	SRR1121242.fastq.gz	Fastqsanger.gz
	SRR1121233.fastq.gz	Fastqsanger.gz

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

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

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

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Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [mRRBS]

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).

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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. 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

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Rspo1 role in mammary gland during pregnancy

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.

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