Evidence map›Paper›PMID 27791005›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Single cell lineage tracing reveals a role for TgfβR2 in intestinal stem cell dynamics and differentiation.

Jared M Fischer, Peter P Calabrese, Ashleigh J Miller, Nina M Muñoz, William M Grady, Darryl Shibata, R Michael Liskay

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

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  4. NADNature communications · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Jared M FischerDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239; fischerj@ohsu.edu.ORCID 0000-0002-0062-0870
Peter P CalabreseDepartment of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.
Ashleigh J MillerDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239.
Nina M MuñozDepartment of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
William M GradyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Department of Medicine, University of Washington Medical School, Seattle, WA 98195.
Darryl ShibataDepartment of Pathology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.
R Michael LiskayDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR 97239.
Oregon Health & Science University · USUniversity of Southern California · USThe University of Texas MD Anderson Cancer Center · USUniversity of Washington Medical Center · US

Funding

Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
GENETIC &MOLECULAR STUDIES OF HUMAN &MOUSE RDNAR01GM036745 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARNHEIM, NORMAN, CALABRESE, PETER PAUL · 1985 to 2017
$8.5M
INTRACHROMOSOMAL RECOMBINATION IN MAMMALIAN CELLSR01GM032741 · NIGMS · YALE UNIVERSITY · PI LISKAY, ROBERT MICHAEL · 1985 to 2013
$1.6M
Cancer and Stem Cell Dynamics in the IntestineK99CA181679 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI FISCHER, JARED MICHAEL · 2014 to 2015
$204k
NCATS NIH HHS UL1 TR000128NCI NIH HHS K99 CA181679NIGMS NIH HHS R01 GM032741NIGMS NIH HHS R01 GM036745
6 · The paper itself

Abstract

Intestinal stem cells (ISCs) are maintained by a niche mechanism, in which multiple ISCs undergo differential fates where a single ISC clone ultimately occupies the niche. Importantly, mutations continually accumulate within ISCs creating a potential competitive niche environment. Here we use single cell lineage tracing following stochastic transforming growth factor β receptor 2 (TgfβR2) mutation to show cell autonomous effects of TgfβR2 loss on ISC clonal dynamics and differentiation. Specifically, TgfβR2 mutation in ISCs increased clone survival while lengthening times to monoclonality, suggesting that Tgfβ signaling controls both ISC clone extinction and expansion, independent of proliferation. In addition, TgfβR2 loss in vivo reduced crypt fission, irradiation-induced crypt regeneration, and differentiation toward Paneth cells. Finally, altered Tgfβ signaling in cultured mouse and human enteroids supports further the in vivo data and reveals a critical role for Tgfβ signaling in generating precursor secretory cells. Overall, our data reveal a key role for Tgfβ signaling in regulating ISCs clonal dynamics and differentiation, with implications for cancer, tissue regeneration, and inflammation.

Indexed as

AnimalsCell DifferentiationCell LineageCell TrackingGene Expression Regulation, DevelopmentalHumansIntestinal MucosaIntestinesMiceMutationPaneth CellsProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IISignal TransductionSingle-Cell AnalysisProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IIintestinal stem celllgr5Paneth cellTgfβTgfβR2

Identifiers

PMID27791005
PMCPMC5087053
OpenAlexW2531384191

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.