Evidence map›Paper›PMID 26519361›Full record

ArticleMolecular systems biology2015

Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo.

Alan J Simmons, Amrita Banerjee, Eliot T McKinley, Cherie' R Scurrah, Charles A Herring, Leslie S Gewin, Ryota Masuzaki, Seth J Karp, Jeffrey L Franklin, Michael J Gerdes and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 42 citations in OpenAlex.

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  20. Single-Cell Computational Strategies for Lineage Reconstruction in Tissue Systems.Cellular and molecular gastroenterology and hepatology · 2018
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Alan J SimmonsEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Amrita BanerjeeEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Eliot T McKinleyEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Cherie' R ScurrahEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Charles A HerringEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Leslie S GewinDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.
Ryota MasuzakiThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Seth J KarpThe Transplant Center and Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Jeffrey L FranklinEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Michael J GerdesLife Sciences Division, GE Global Research, Niskayuna, NY, USA.
Jonathan M IrishDepartments of Cancer Biology, and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Robert J CoffeyEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA.
Ken S LauEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN, USA Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA Department of Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, USA ken.s.lau@vanderbilt.edu.
Vanderbilt University Medical Center · USGE Global Research (United States) · USVA Tennessee Valley Healthcare System · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt/Meharry Initiative for Minority Student DvptR25GM062459 · NIGMS · VANDERBILT UNIVERSITY · PI VELEZ EDWARDS, DIGNA R · 2002 to 2020
$10.4M
TRANSFORMING GROWTH FACTORS IN COLONIC NEOPLASIAR01CA046413 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 1988 to 2016
$8.8M
Multidisciplinary Training in Basic and Translational Imaging of CancerR25CA092043 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MANNING, HENRY CHARLES · 2001 to 2015
$6.6M
Training Program in Stem Cell and Regenerative Developmental BiologyT32HD007502 · NICHD · VANDERBILT UNIVERSITY · PI WRIGHT, CHRISTOPHER V · 1997 to 2022
$5.4M
Validation of a single cell multiplexed in-situ biomarker analysis platform for pR01CA174377 · NCI · GENERAL ELECTRIC GLOBAL RESEARCH CTR · PI COFFEY, ROBERT J., GERDES, MICHAEL · 2012 to 2016
$3.7M
MOLECULAR PARASITOLOGY TRAINING PROGRAMT32AI007281 · NIAID · MEHARRY MEDICAL COLLEGE · PI NDE, PIUS N · 1985 to 2025
$3.2M
Roles for Lrig1 in Intestinal NeoplasiaR01CA151566 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2010 to 2016
$2.1M
BMP Signaling--A Therapeutic Target in Liver DiseaseR01DK081387 · NIDDK · VANDERBILT UNIVERSITY · PI KARP, SETH J · 2010 to 2014
$1.7M
NCATS NIH HHS 2UL1TR000445NCATS NIH HHS UL1 TR000445NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA095103NCI NIH HHS R00 CA143231NCI NIH HHS R01 CA046413NCI NIH HHS R01 CA151566NCI NIH HHS R01 CA174377NCI NIH HHS R25 CA092043NIAID NIH HHS T32 AI007281NICHD NIH HHS T32 HD007502NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK081387NIDDK NIH HHS R01 DK81387NIGMS NIH HHS R25 GM062459
6 · The paper itself

Abstract

Understanding heterogeneous cellular behaviors in a complex tissue requires the evaluation of signaling networks at single-cell resolution. However, probing signaling in epithelial tissues using cytometry-based single-cell analysis has been confounded by the necessity of single-cell dissociation, where disrupting cell-to-cell connections inherently perturbs native cell signaling states. Here, we demonstrate a novel strategy (Disaggregation for Intracellular Signaling in Single Epithelial Cells from Tissue-DISSECT) that preserves native signaling for Cytometry Time-of-Flight (CyTOF) and fluorescent flow cytometry applications. A 21-plex CyTOF analysis encompassing core signaling and cell-identity markers was performed on the small intestinal epithelium after systemic tumor necrosis factor-alpha (TNF-α) stimulation. Unsupervised and supervised analyses robustly selected signaling features that identify a unique subset of epithelial cells that are sensitized to TNF-α-induced apoptosis in the seemingly homogeneous enterocyte population. Specifically, p-ERK and apoptosis are divergently regulated in neighboring enterocytes within the epithelium, suggesting a mechanism of contact-dependent survival. Our novel single-cell approach can broadly be applied, using both CyTOF and multi-parameter flow cytometry, for investigating normal and diseased cell states in a wide range of epithelial tissues.

Indexed as

MAP Kinase Signaling SystemSignal TransductionSingle-Cell AnalysisApoptosisEnzyme ActivationEpithelial CellsHumansTumor Necrosis Factor-alphaTumor Necrosis Factor-alphaapoptosisCyTOFepithelial signalingsingle‐cell biologyTNF

Identifiers

PMID26519361
PMCPMC4631206
OpenAlexW2180807405

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.