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Series GSE61198 Query DataSets for GSE61198
Status Public on Sep 02, 2015
Title Distinct EMT programs control normal stem cells and cancer stem cells of mammary tissue
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cancer stem cells (CSCs) are proposed to be responsible for metastatic dissemination and clinical relapse in a variety of cancers. Analogies between CSCs and normal tissue stem cells (SC) has led to the notion that CSCs often co-opt the normal SC program of their tissue-of-origin. The cell-biological program termed epithelial-mesenchymal transition (EMT) has been found to encourage entrance of normal and neoplastic mammary cells into the corresponding SC states. Using genetically engineered knock-in reporter mouse lines, we demonstrate that in the murine mammary lineage, the paralogous EMT-inducing transcription factors Snail and Slug, are selectively exploited by CSCs and normal SCs respectively. Slug, when expressed at physiological levels, only activates a partial EMT program and is dispensable in CSCs. In contrast, Snail drives a far more complete transition into the mesenchymal state and controls both tumor-initiation and metastatic dissemination. Consistent with their functional distinctions, Snail controls far more target genes than Slug, and their distinct functions are determined by their divergent N-terminal domains. Our findings underscore fundamental distinctions between the SC program operating in normal and neoplastic SCs, and hint for potential avenues of selective therapeutic elimination of breast CSCs.
Overall design We sought to understand differential ability to activate the EMT program in breast cancer cells by transcription factors Snail and Slug. Hence, we mapped genome-wide Snail and Slug binding sites in murine MMTV-PyMT breast cancer cell lines that express high level of Snail or high level of Slug respectively. Specifically, we performed Snail ChIP seq in the mesenchymal pBl.3G cells, and Slug ChIP-seq in the epithelial pBl.1G cells.
Contributor(s) Ye X, Tam WL, Weinberg RA
Citation(s) 26331542
Submission date Sep 08, 2014
Last update date May 15, 2019
Contact name Xin Ye
Organization name Whitehead Institute
Department Whitehead Institute
Lab Robert Weinberg
Street address 9 Cambridge Center
City Cambridge
State/province MA
ZIP/Postal code 02143
Country USA
Platforms (2)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (4)
GSM1499411 pB1.1G input DNA
GSM1499412 pB1.3G input DNA
GSM1499413 pBl.1G Slug ChIP
BioProject PRJNA260499
SRA SRP046313

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Supplementary file Size Download File type/resource
GSE61198_RAW.tar 990.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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