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Title: Cell type-specific chromatin states differentially prime squamous cell carcinoma tumor-initiating cells for epithelial to mesenchymal transition [expression 1]      
keywords:
Transcriptome or Gene expression
ID:
PRJNA348518
description:
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness and resistance to therapy. The reason why some tumors undergo EMT and other not might reflect intrinsic properties of their cell of origin, although this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show cell type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from intrafollicular epidermis (IFE) are generally well-differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT. Overall design: KrasG12D and YFP expression combined with deletion of p53 were induced in Hair Follicle Stem cells (SCs) and their progeny using Lgr5CREER/KRasG12D/p53fl/fl/Rosa-YFP mice, and in the Intra Follicular Epidermis and the infundibulum using K14CREER/KRasG12D/p53fl/fl/Rosa-YFP mice by intraperitoneal tamoxifen injection. Cells were harvested and compared prior oncogenic hits and in fully grown tumours.
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA348518
authentication:
none
authorization:
none
ID:
pmid:27889319
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject