Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate
<p>Abstract</p> <p>Background</p> <p>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 int...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2008-12-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/9/591 |
| _version_ | 1811329395618480128 |
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| author | Zvelebil Marketa Mitsopoulos Costas Grigoriadis Anita Magnay Fiona-Ann Regan Joseph L Kendrick Howard Smalley Matthew J |
| author_facet | Zvelebil Marketa Mitsopoulos Costas Grigoriadis Anita Magnay Fiona-Ann Regan Joseph L Kendrick Howard Smalley Matthew J |
| author_sort | Zvelebil Marketa |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>Sox6</it>, 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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-04-13T15:43:08Z |
| format | Article |
| id | doaj.art-7ec43fe8c8d447fa914c3b5d8fb4b7b2 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-04-13T15:43:08Z |
| publishDate | 2008-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-7ec43fe8c8d447fa914c3b5d8fb4b7b22022-12-22T02:41:05ZengBMCBMC Genomics1471-21642008-12-019159110.1186/1471-2164-9-591Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fateZvelebil MarketaMitsopoulos CostasGrigoriadis AnitaMagnay Fiona-AnnRegan Joseph LKendrick HowardSmalley Matthew J<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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, <it>Sox6</it>, 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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/9/591 |
| spellingShingle | Zvelebil Marketa Mitsopoulos Costas Grigoriadis Anita Magnay Fiona-Ann Regan Joseph L Kendrick Howard Smalley Matthew J Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate BMC Genomics |
| title | Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| title_full | Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| title_fullStr | Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| title_full_unstemmed | Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| title_short | Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| title_sort | transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate |
| url | http://www.biomedcentral.com/1471-2164/9/591 |
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