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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Histone methylation profiles of prospectively isolated mammary epithelial subpopulations

ABSTRACT: In this study we mapped H3K27me3, H3K4me3 and H3K9me2 marks in three mammary epithelial subsets: MaSC/basal (MS), luminal progenitor (LP) and mature luminal (ML) in the steady-state. In addition, profiles were generated for H3K4me3 and H3K27me3 marks in the MaSC/basal and luminal populations from the glands of ovariectomized or mid-pregnant (12.5 days) mice as well as from control virgin mice. We used ChIPseq analysis to determine histone modification marks in the MS, LP and ML subsets in the steady-state. We then determined the histone modification profiles of MS and sorted luminal (Lum) cells from pregnant (12.5 dP) or ovariectomized (OVX) mice and compared these with the profiles of control virgin mice in order to study the effect of hormones on the mammary epigenomes.

ORGANISM(S): Mus musculus

SUBMITTER: Wei Shi

PROVIDER: E-GEOD-43212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global changes in the mammary epigenome are induced by hormonal cues and coordinated by Ezh2.

Pal Bhupinder B Bouras Toula T Shi Wei W Vaillant François F Sheridan Julie M JM Fu Naiyang N Breslin Kelsey K Jiang Kun K Ritchie Matthew E ME Young Matthew M Lindeman Geoffrey J GJ Smyth Gordon K GK Visvader Jane E JE

Cell reports 20130131 2

The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial subpopulations in different states. The marked differences in H3K27 trimethylation between subpopulations in the adult gland suggest that epithelial cell-fate decisions are orchestrated by polycomb-complex-mediated repression. Remarkably, the mammary e ...[more]

PMID: 23375371

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Histone methylation profiles of prospectively isolated mammary epithelial subpopulations

Project description:In this study we mapped H3K27me3, H3K4me3 and H3K9me2 marks in three mammary epithelial subsets: MaSC/basal (MS), luminal progenitor (LP) and mature luminal (ML) in the steady-state. In addition, profiles were generated for H3K4me3 and H3K27me3 marks in the MaSC/basal and luminal populations from the glands of ovariectomized or mid-pregnant (12.5 days) mice as well as from control virgin mice.

2013-02-20 | GSE43212 | GEO

Gene expression profiles of normal mouse mammary cell subpopulations FACS sorted based on expression of biomarkers

Project description:To delineate epithelial subpopulations in mouse mammary tissue, hematopoietic and endothelial cells were depleted from freshly isolated cell suspensions derived from mammary glands using fluorescence-activated cell sorting. The resultant Lin- population was fractionated into four distinct subpopulations using antibodies against CD29, CD24 and CD61. Based on the immunohistochemical phenotype, and in vivo and in vitro functional assays, these subpopulations were identified as fibroblast-containing stromal (CD29loCD24-), mammary stem cell (MaSC)-enriched (CD29hiCD24+CD61+), luminal progenitor (CD29loCD24+CD61+), and mature luminal (CD29loCD24+CD61-) cell subpopulations. Microarray profiling was used to derive gene expression signatures of these 4 subpopulations. The four mammary cell subpopulations were found to have distinct gene expression profiles. Four mammary cell subpopulations from 3-5 pooled mouse tissues were analysed. MS is for the MaSC-enriched cell subpopulation. LP is for the Luminal Progenitor subpopulation. ML is for the Mature Luminal subpopulation.

2010-03-20 | E-GEOD-19446 | biostudies-arrayexpress

Transcriptome characterization of IFNa response in MaSC and luminal progenitor cells

Project description:Transcriptome response to IFNa treatment in MaSC, Luminal progenitor cells were studied. The MaSC, Luminal progenitor cells enriched subpopulations were sorted based on CD24/CD29 expression from mammary epithelial cells of virgin female mice . (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035). The cells were cultured in mammosphere condition in vitro and treated with Ifna for 8 days. The total RNA samples are collected and compared using microarray analysis.

2017-05-05 | GSE93068 | GEO

Expression data from sorted control and Pygo2-null mouse mammary stem/basal cells

Project description:Skin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development. The FACS sorted mammary stem cell (MaSC)/basal population from Pygo2 SSKO mammary gland displays biased differentiation towards luminal/alveolar lineage in vitro, and reduced regeneration rate of new mammary gland in vivo To gain the insight into gene expression profiles in control and Pygo2 SSKO mammary epithelial cells (MECs), we sorted the freshly isolated mouse MECs into MaSC/basal (Lin-CD29hiCD24+) and mature luminal population (Lin-CD29lowCD24+CD61-), and extract total RNA for cDNA microarray analysis

2013-09-05 | E-GEOD-45826 | biostudies-arrayexpress

Loss of neuronal 3D chromatin organization causes transcriptional and behavioral deficits related to serotonergic dysfunction [ChIP-seq]

Project description:The interior of the neuronal cell nucleus is a highly organized 3-dimensional (3D) structure in which regions of the genome that are millions of bases apart participate in specialized sub-structures with dedicated functions. To investigate neuronal chromatin organization and dynamics in vivo, we generated bitransgenic mice that express histone GFP-tagged H2B in principal neurons of the forebrain. Surprisingly, the expression of this chimeric histone in mature neurons causes chromocenter declustering and disrupts the association of heterochromatin with the nuclear lamina. The loss of these structures does not affect neuronal viability but is associated with specific transcriptional and behavioral deficits related to serotonergic dysfunction. Overall, our results demonstrate that the 3D-organization of chromatin in the neuronal nucleus supports an additional level of epigenetic regulation of gene expression that critically influences neuronal function and indicate that some loci associated with neuropsychiatric disorders may be particularly sensitive to changes in chromatin architecture. Genome-wide profiling by high throughput sequencing of H3K27me3 in the adult hippocampus of CaMKII-tTA/tetO-H2BGFP (H2BGFP) and their wild-type littermates mice (WT). Chromatin immunoprecipitation (ChIP) was carried out using pooled hippocampal tissue from 3 mice (one hippocampus per mouse). One DNA library was constructed per genotype. Each DNA library was prepared from pooled immunoprecipitated DNA from 4 independent ChIP assays. In total, tissue from 12 different mice was used to prepare each DNA library. 60% of a lane was used to perform single end (1x50bp) multiplex sequencing in HiSeq 2500 apparatus (Illumina). Each library, was sequenced in duplicate (in two independent sequencing runs. Technical replicates).

2014-07-18 | E-GEOD-56809 | biostudies-arrayexpress

Microarray expression profiling of distinct subsets of mouse mammary epithelial cells

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

Microarray expression profiling data for Trp53-null mammary epithelial cells and tumors from a mouse model with a K8+ luminal cell origin

Project description:Mammary epithelium is hierarchically organized, with multipotent basal mammary stem cells (MaSCs) producing both luminal and basal cells during development or upon transplantation. Recent studies suggested that most breast cancers might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CAH1047R, could induce multipotency in committed luminal cells. p53 is the most commonly mutated gene in human breast cancer; in particular, its inactivating mutations are found in most triple-negative breast cancers, raising a question as to whether p53-loss plays a key role in acquisition of MaSC-like properties by luminal cells. By in situ lineage tracing, we found that induced loss of p53 in Keratin 8 (K8)+ luminal cells led to their clonal expansion, in part due to increased proliferation, but did not directly affect their luminal identity. Expansion of luminal cells, in particular oestrogen receptor-positive luminal cells, was observed 3-4 weeks after induced p53-loss, which was accompanied by increased expression of cell cycle genes and downregulation of genes related to immune microenvironment, p53 downstream pathway and apoptosis control. All induced mice eventually developed mammary tumours with 9qA1 (Yap1) amplification and/or 6qA2 (Met) amplification. The resulting tumours exhibited a MaSC-like expression signature and most closely resembled Claudin-Low breast cancer. Overall, these data suggest that although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumours with loss of luminal identity. Our data also suggest that Claudin-Low breast cancer can originate from luminal cells, possibly upon transition through a basal-like state.

2016-12-20 | GSE77496 | GEO

∆Np63 regulates stem cell activity in mammary gland development

Project description:MaSC, luminal progenitor enriched subpopulations and total MECs as well, were isolated from both wild type and ∆Np63 KO heterozygous mouse and the transcriptome profiles were determined and compared.

2014-08-19 | GSE47417 | GEO

Transcriptome profiles of mouse mammary stem cells and progenitor cells

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

microRNA expression profiles of distinct human mammary epithelial cell types

Project description:RNA samples were prepared from freshly sorted mammary cell subpopulations (MaSC/basal-enriched, luminal progenitor, mature luminal and stromal) from five human donors. High throughput RT-PCR was used to measure the global microRNA expression profiles of each cell subpopulation. The expression profiles were compared between cell subpopulations to gain insight into the regulation of lineage-restricted genes.

2016-02-20 | GSE67054 | GEO

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