Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (RNA-Seq I)

ABSTRACT: After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Mouse skin squamouse cell carcinoma (SCC) tumor-initiating stem cells (SCC-SC), hair follicle stem cells (HF-SC) and epidermal stem cells (Epi-SC) were FACS-prufied for RNA-sequencing.

ORGANISM(S): Mus musculus

SUBMITTER: Hanseul Yang

PROVIDER: E-GEOD-72146 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

ETS family transcriptional regulators drive chromatin dynamics and malignancy in squamous cell carcinomas.

Yang Hanseul H Schramek Daniel D Adam Rene C RC Keyes Brice E BE Wang Ping P Zheng Deyou D Fuchs Elaine E

eLife 20151121

Tumor-initiating stem cells (SCs) exhibit distinct patterns of transcription factors and gene expression compared to healthy counterparts. Here, we show that dramatic shifts in large open-chromatin domain (super-enhancer) landscapes underlie these differences and reflect tumor microenvironment. By in vivo super-enhancer and transcriptional profiling, we uncover a dynamic cancer-specific epigenetic network selectively enriched for binding motifs of a transcription factor cohort expressed in squam ...[more]

PMID: 26590320

Similar Datasets

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (ChIP-Seq I)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Mouse skin squamouse cell carcinoma (SCC) tumor-initiating stem cells (SCs) were FACS-purified for ChIP-sequencing.

2015-11-22 | E-GEOD-72145 | biostudies-arrayexpress

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (RNA-Seq II)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Epidermal basal stem cells from ETS2(T72D) super-activated epidermis and normal epidermis were FACS-prufied for RNA-sequencing.

2015-11-22 | E-GEOD-74868 | biostudies-arrayexpress

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas (ChIP-Seq II)

Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Control and ETS2(T72D) super-activated epidermal basal stem cells were FACS-purified for ChIP-sequencing.

2015-11-22 | E-GEOD-74867 | biostudies-arrayexpress

RNA-seq in squamous cell carcinoma stem cells in the presence or absence of TGF-beta signaling

Project description:We performed RNA-seq on purified squamous cell carcinoma stem cells (SCC-SCs) from primary mouse skin tumors transduced with TGF-beta reporter. SCC-SCs were purified based on cell surface marker expression integrin alpha6 and CD44, after lineage negative selection, and separated by fluorescent TGF-beta reporter expression.

2015-02-27 | E-GEOD-64867 | biostudies-arrayexpress

miRNA expression profiling in squamous cell carcinoma (SCC)

Project description:Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. We recently identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC, and demonstrated that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Reduced levels of GRHL3 and its target gene PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data defines the miR-21-GRHL3-PTEN-axis as a critical tumor suppressor pathway in SCC. Total RNA was isolated from two SCC primary tissue samples and their matched normal skin controls.

2013-01-18 | E-GEOD-32868 | biostudies-arrayexpress

Cancer stem cell features shift during skin squamous cell carcinoma progression

Project description:Cancer stem cells (CSCs) play a key role in tumour growth and metastasis. Although an expansion of CSC population was previously described in advanced cutaneous squamous cell carcinoma (SCC), it remains unknown whether CSC regulatory mechanisms also change through tumour progression to promote malignancy. Here, we generate mouse models of skin SCCs to study alterations in CSC regulation over progression. We found that features of CSCs change at late stage of progression, correlating with a switch from epithelial to mesenchymal tumour shape. beta-catenin and EGFR signalling are down-regulated, whereas autocrine FGFR1 and PDGFR alpha pathways are up-regulated in CSCs of advanced tumours. Inhibition of FGFR and PDGFR signalling repress malignant SCCs growth and metastasis, respectively. An enhanced epithelial-to-mesenchymal transition (EMT) program and over-expression of PDGFR alpha and FGFR1 are observed in malignant human skin SCCs, suggesting that these pathways are also induced over human SCC progression. Therefore, uncover signalling pathways controlling CSCs at specific stage of progression may improve the selection of more accurate targeted therapeutic strategies according to tumour stage, blocking SCC relapse and metastasis. Mouse models of skin SCCs progression were first generated. For that, individual samples of spontaneous or DMBA-TPA induced skin SCCs generated in K14-HPV16 mice were orthotopically engrafted in immunodeficient mice and then serially transplanted, generating lineages in which the progression from WD-SCCs to PD-SCCs was observed. Then, tumour cells expressing CD34 and alpha 6-integrin, previously identified as cutaneous cancer stem cells, were isolated by flow cytometry-sorter from WD-SCCs and PD-SCCs of different tumour lineages. RNA extraction and hybridization on Affymetrix microarrays was carried out to compare whole gene profiling of these populations of CSCs.

2016-01-08 | E-GEOD-59439 | biostudies-arrayexpress

ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-21 | E-GEOD-72147 | biostudies-arrayexpress

Hierarchy within the mammary STAT5-driven Wap super-enhancer

Project description:Super-enhancers comprise of dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate their role in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-Seq for the master regulator STAT5, the glucocorticoid receptor, H3K27ac and MED1, identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5 binding sites within its three constituent enhancers. Individually, only the most distal site displayed significant enhancer activity. However, combinatorial mutations showed that the 1,000-fold gene induction relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer, suggesting an enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insight into the complexity of cell-specific and hormone-regulated genes. ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, RNA Pol II, and H3K4me3 in wild type (WT) mammary tissues at day one of lactation (L1), and ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, and H3K4me3 in WT mammary tissues at day 13 of pregnancy (p13). ChIP-Seq for STAT5A, GR, H3K27a in Wap-delE1a, -delE1b, -delE1c, -delE2 and -delE3 mutant mammary tissues at L1, and ChIP-Seq for NFIB and ELF5 in Wap-delE1b and -delE1c mutant mammary tissues at L1. ChIP-Seq for H3K4me3 in mammary-epthelial cells at p13 and L1. DNase-seq in WT mammary tissues at L1 and DNase-seq in Wap-delE1a, -delE1c, and -delE3 mutant mammary tissues at L1.

2016-05-31 | E-GEOD-74826 | biostudies-arrayexpress