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Title:
Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate | BMC Genomics
Description:
Background Understanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out. Results A whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these, Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage. Conclusion The mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence of a novel functional cell type within the gland, that the basal/myoepithelial cells are key regulators of paracrine signalling and that there is a complex network of differentially expressed transcription factors controlling mammary epithelial cell fate. These data will form the basis for understanding not only cell fate determination and cellular homeostasis in the normal mammary epithelium but also the contribution of different mammary epithelial cell types to the etiology and molecular pathology of breast disease.
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Keywords {π}
cells, luminal, cell, mammary, expression, pubmed, genes, gene, google, scholar, cas, epithelial, expressed, analysis, population, network, data, populations, additional, basalmyoepithelial, cancer, file, gland, mouse, sox, breast, interactions, differentially, nodes, factors, epithelium, figure, fate, receptor, signalling, krt, interaction, estrogen, identified, sca, qpcr, transcription, basal, central, gfp, modules, stem, transcriptional, fat, compared,
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uk/collaborations/smalley/pops_gene_exp/miame/kendrick_miame_checklist sry-related high-mobility-group box open access article milk-secreting lobulo-alveolar structures cd24+/low sca-1- basal/myoepithelial guanine-nucleotide exchange factor acousto-optical beam splitter quantitative real-time rtpcr cdc2/cyclinb1 kinase inhibitors lymphoid-myeloid lineage diversification estrogen receptor-alpha knockout shaping t-cell activation cd24+/high sca-1+ cells cd24+/high sca-1- cells cell proliferation-related proteins anita grigoriadis transcription factors l-sox5 author information authors eph-ephrin bidirectional signaling luminal cell-fate commitment platelet-derived growth factor cd24+/low sca-1- cells fluorescence-activated cell sorting cd24+/high sca-1+ population double negative cells cell-type specific genes robust multi-array analysis basal/myoepithelial cell marker anti-cd24-pe-cy5 cd24+/high sca-1+ regions phycoerythrin-cy5 pe-cy7 key cell-intrinsic factors lineage-specific transcription factors article download pdf basal/myoepithelial cell dataset luminal epithelial fraction wild-type cells failed array-based expression pattern bmc cell biol cell stem cell estrogen responsive profile anti-sca-1 staining pattern anti-cd45-pe-cy5 basal/myoepithelial cell population g-protein coupled receptors basal/myoepithelial interaction map anti-cd45-pe-cy7 constitutive igf1/igf2 stimulation de-differentiation event resulting stem/progenitor fraction
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headline:Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate
description:Understanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out. A whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these, Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage. The mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence of a novel functional cell type within the gland, that the basal/myoepithelial cells are key regulators of paracrine signalling and that there is a complex network of differentially expressed transcription factors controlling mammary epithelial cell fate. These data will form the basis for understanding not only cell fate determination and cellular homeostasis in the normal mammary epithelium but also the contribution of different mammary epithelial cell types to the etiology and molecular pathology of breast disease.
datePublished:2008-12-08T00:00:00Z
dateModified:2008-12-08T00:00:00Z
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Mammary Epithelial Cell
Mammary Epithelium
Luminal Cell
Luminal Epithelial Cell
Double Negative Cell
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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headline:Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate
description:Understanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out. A whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these, Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage. The mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence of a novel functional cell type within the gland, that the basal/myoepithelial cells are key regulators of paracrine signalling and that there is a complex network of differentially expressed transcription factors controlling mammary epithelial cell fate. These data will form the basis for understanding not only cell fate determination and cellular homeostasis in the normal mammary epithelium but also the contribution of different mammary epithelial cell types to the etiology and molecular pathology of breast disease.
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dateModified:2008-12-08T00:00:00Z
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Mammary Epithelial Cell
Mammary Epithelium
Luminal Cell
Luminal Epithelial Cell
Double Negative Cell
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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