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Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.

Cell stem cell | 2017

Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular 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 that 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.

Pubmed ID: 27889319 RIS Download

Additional research tools detected in this publication

Associated grants

  • Agency: Worldwide Cancer Research, United Kingdom
    Id: 15-0270
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR066703
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR071435

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This is a list of tools and resources that we have found mentioned in this publication.


Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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Picard (tool)

RRID:SCR_006525

Java toolset for working with next generation sequencing data in the BAM format.

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Bowtie 2 (tool)

RRID:SCR_016368

Ultrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

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ZEB2-human (antibody)

RRID:AB_10603840

This polyclonal targets ZEB2

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ZEB1 IHC Antibody (antibody)

RRID:AB_1659852

This unknown targets ZEB1

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Vimentin antibody [EPR3776] (antibody)

RRID:AB_10562134

This monoclonal targets Vimentin antibody [EPR3776]

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SOX2 antibody [EPR3131] (antibody)

RRID:AB_10585428

This monoclonal targets SOX2 antibody [EPR3131]

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B6.129P2-Trp53tm1Brn/J (organism)

RRID:IMSR_JAX:008462

Mus musculus with name B6.129P2-Trp53tm1Brn/J from IMSR.

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B6.129P2-Lgr5tm1(cre/ERT2)Cle/J (organism)

RRID:IMSR_JAX:008875

Mus musculus with name B6.129P2-Lgr5tm1(cre/ERT2)Cle/J from IMSR.

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STOCK Tg(KRT14-cre/ERT)20Efu/J (organism)

RRID:IMSR_JAX:005107

Mus musculus with name STOCK Tg(KRT14-cre/ERT)20Efu/J from IMSR.

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B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (organism)

RRID:IMSR_JAX:006148

Mus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.

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K:Molv NIH/3T3 (cell line)

RRID:CVCL_6662

Cell line K:Molv NIH/3T3 is a Transformed cell line with a species of origin Mus musculus (Mouse)

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HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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HOMER (software resource)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

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BD FACSDiva Software (software resource)

RRID:SCR_001456

A collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.

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AxioVision Imaging System (software resource)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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ZEB2-human (antibody)

RRID:AB_10603840

This polyclonal targets ZEB2

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Vimentin antibody [EPR3776] (antibody)

RRID:AB_10562134

This monoclonal targets Vimentin antibody [EPR3776]

View all literature mentions

SOX2 antibody [EPR3131] (antibody)

RRID:AB_10585428

This monoclonal targets SOX2 antibody [EPR3131]

View all literature mentions

ZEB1 IHC Antibody (antibody)

RRID:AB_1659852

This unknown targets ZEB1

View all literature mentions