Evidence map›Paper›PMID 33444816›Full record

ArticleCellular and molecular gastroenterology and hepatology2021

scRNA-Seq Reveals New Enteric Nervous System Roles for GDNF, NRTN, and TBX3.

Christina M Wright, Sabine Schneider, Kristen M Smith-Edwards, Fernanda Mafra, Anita J L Leembruggen, Michael V Gonzalez, Deepika R Kothakapa, Jessica B Anderson, Beth A Maguire, Tao Gao and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
16.5field-weighted citation impact, top 1% 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

64 citing papers in PubMed, 105 citations in OpenAlex.

  1. Resolving cell lineages and gene functions in the developing mouse gastrointestinal tract using in utero transduction.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Time-resolved morphological and transcriptomic characterization of early enteric neuron subtype emergence in chick.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  8. Combinatorial multiomic analysis from a pedigree of Sox10bioRxiv : the preprint server for biology · 2025
    Article
  9. Joint disruption ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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4 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 2 countries.

Christina M WrightDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Sabine SchneiderDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Kristen M Smith-EdwardsDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, Pennsylvania.
Fernanda MafraCenter for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
Anita J L LeembruggenDepartment of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Michael V GonzalezCenter for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
Deepika R KothakapaDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Jessica B AndersonDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Beth A MaguireDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Tao GaoDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Tricia A MissallDepartment of Dermatology, University of Florida, Gainesville, Florida.
Marthe J HowardDepartment of Neurosciences, University of Toledo Health Sciences Campus, Toledo, Ohio.
Joel C BornsteinDepartment of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Brian M DavisDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, Pennsylvania.
Robert O HeuckerothDepartment of Pediatrics, Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: heuckerothr@chop.edu.
Children's Hospital of Philadelphia · USThe University of Melbourne · AUUniversity of Pittsburgh · USUniversity of Florida · USUniversity of Toledo · US

Funding

Anatomical-Functional Mapping of Enteric Neural CircuitsOT2OD023859 · OD · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI HOWARD, MARTHE J · 2016 to 2019
$6.9M
Training in Mechanisms and Clinical Presentation of PainT32NS073548 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jami Lynn Saloman, BRADLEY K. TAYLOR · 2012 to 2026
$3.1M
Molecular and Functional Analysis of Hirschsprung Defects in Humans and MouseR01DK122798 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERS, KATHRYN MARIE, DAVIS, BRIAN M · 2020 to 2023
$2.8M
Cross-talk between the colon epithelium, colon afferents and sympathetic neurons regulate pain in the normal and inflamed colonR01DK124955 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALBERS, KATHRYN MARIE, DAVIS, BRIAN M · 2020 to 2023
$1.8M
Identifying Defects in the ENS Connectome of Hirschsprung Disease ModelsF32DK120115 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SMITH-EDWARDS, KRISTEN MICHELLE · 2019 to 2021
$156k
Characterization of the Role of Dlx1 and Dlx2 in the Enteric Nervous SystemF30DK117546 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WRIGHT, CHRISTINA MARIE · 2018 to 2019
$64k
NIDDK NIH HHS F30 DK117546NIDDK NIH HHS F32 DK120115NIDDK NIH HHS R01 DK122798NIDDK NIH HHS R01 DK124955NIH HHS OT2 OD023859NINDS NIH HHS T32 NS073548
6 · The paper itself

Abstract

BACKGROUND AND

aimsBowel function requires coordinated activity of diverse enteric neuron subtypes. Our aim was to define gene expression in these neuron subtypes to facilitate development of novel therapeutic approaches to treat devastating enteric neuropathies, and to learn more about enteric nervous system function.

methodsTo identify subtype-specific genes, we performed single-nucleus RNA-seq on adult mouse and human colon myenteric plexus, and single-cell RNA-seq on E17.5 mouse ENS cells from whole bowel. We used immunohistochemistry, select mutant mice, and calcium imaging to validate and extend results.

resultsRNA-seq on 635 adult mouse colon myenteric neurons and 707 E17.5 neurons from whole bowel defined seven adult neuron subtypes, eight E17.5 neuron subtypes and hundreds of differentially expressed genes. Manually dissected human colon myenteric plexus yielded RNA-seq data from 48 neurons, 3798 glia, 5568 smooth muscle, 377 interstitial cells of Cajal, and 2153 macrophages. Immunohistochemistry demonstrated differential expression for BNC2, PBX3, SATB1, RBFOX1, TBX2, and TBX3 in enteric neuron subtypes. Conditional Tbx3 loss reduced NOS1-expressing myenteric neurons. Differential Gfra1 and Gfra2 expression coupled with calcium imaging revealed that GDNF and neurturin acutely and differentially regulate activity of ∼50% of myenteric neurons with distinct effects on smooth muscle contractions.

conclusionSingle cell analyses defined genes differentially expressed in myenteric neuron subtypes and new roles for TBX3, GDNF and NRTN. These data facilitate molecular diagnostic studies and novel therapeutics for bowel motility disorders.

Indexed as

Gene Expression RegulationAdultAgedAged, 80 and overAnimalsBiomarkersEnteric Nervous SystemFemaleGlial Cell Line-Derived Neurotrophic FactorHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedNeurturinBiomarkersGlial Cell Line-Derived Neurotrophic FactorNeurturinNRTN protein, humanT-Box Domain ProteinsTBX3 protein, humanCalcium ImagingHuman and Mouse ColonPou3f3 (Brn1)Transcription Factors

Identifiers

PMID33444816
PMCPMC8099699
OpenAlexW3120659488

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.