Evidence map›Paper›PMID 33010250›Full record

ArticleGastroenterology2021

Combinatorial Transcriptional Profiling of Mouse and Human Enteric Neurons Identifies Shared and Disparate Subtypes In Situ.

Aaron A May-Zhang, Eric Tycksen, Austin N Southard-Smith, Karen K Deal, Joseph T Benthal, Dennis P Buehler, Mike Adam, Alan J Simmons, James R Monaghan, Brittany K Matlock and 4 more

Open access · greenAbstract readComparative Study
In one paragraph

Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
14.3field-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

76 citing papers in PubMed, 120 citations in OpenAlex.

  1. Article
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  11. Methods to Isolate Enteric Glia from hPSC-Derived Enteric Ganglioids.Methods in molecular biology (Clifton, N.J.) · 2026
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  15. Purinergic P2YPurinergic signalling · 2025
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  16. Article
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Aaron A May-ZhangDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Eric TycksenGenome Technology Access Center, McDonnell Genome Institute, St Louis, Missouri.
Austin N Southard-SmithEpithelial Biology Center and the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Karen K DealDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Joseph T BenthalDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Dennis P BuehlerDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Mike AdamUniversity of Cincinnati Children's Medical Hospital Research Center, Cincinnati, Ohio.
Alan J SimmonsEpithelial Biology Center and the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
James R MonaghanNortheastern University, Department of Biology, Boston, Massachusetts.
Brittany K MatlockOffice of Shared Resources, Vanderbilt University School of Medicine, Nashville, Tennessee.
David K FlahertyOffice of Shared Resources, Vanderbilt University School of Medicine, Nashville, Tennessee.
S Steven PotterUniversity of Cincinnati Children's Medical Hospital Research Center, Cincinnati, Ohio.
Ken S LauEpithelial Biology Center and the Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
E Michelle Southard-SmithDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: michelle.southard-smith@vanderbilt.edu.
Vanderbilt University · USCincinnati Children's Hospital Medical Center · USJames S. McDonnell Foundation · USNortheastern University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3M
TRAINING IN GASTROENTEROLOGYT32DK007673 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 1992 to 2026
$8.4M
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory diseaseR01DK103831 · NIDDK · VANDERBILT UNIVERSITY · PI LAU, KEN S · 2016 to 2024
$4.4M
Optical Nanosensors Detect Neurotransmitter Release in the Peripheral Nervous SystemOT2OD024909 · OD · NORTHEASTERN UNIVERSITY · PI MONAGHAN, JAMES R · 2017 to 2021
$2.1M
ENSMAP: Molecular and Functional Mapping of the Enteric Nervous SystemOT2OD023850 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SOUTHARD-SMITH, E MICHELLE · 2016 to 2019
$2.0M
LSM880-Airyscan Confocal Microscope for Large Shared ResourceS10OD021630 · OD · VANDERBILT UNIVERSITY · PI WELLS, K. SAM · 2016 to 2016
$560k
NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA091842NICHD NIH HHS P50 HD103537NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK103831NIDDK NIH HHS T32 DK007673NIDDK NIH HHS U24 DK059637NIH HHS OT2 OD023850NIH HHS OT2 OD024909NIH HHS S10 OD021630
6 · The paper itself

Abstract

BACKGROUND &

aimsThe enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (ENs). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions.

methodsHuman myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA sequencing. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA sequencing, totaling more than 4 billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse single-nucleus RNA sequencing data. Comparative informatics between human and mouse data sets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction.

resultsSeveral EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of 1 or more marker genes.

conclusionsOur combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human gastrointestinal studies.

Indexed as

Species SpecificityAdolescentAdultAnimalsCell DifferentiationCell NucleusColonDisease Models, AnimalDuodenumEnteric Nervous SystemFemaleGastrointestinal DiseasesGastrointestinal MotilityGene Expression RegulationHumansIleumENSEnteric Nervous SystemHCRIn Situ Hybridization Chain ReactionRNA-SeqRNA SequencingSingle-Nucleus RNA-Seq

Identifiers

PMID33010250
PMCPMC7878294
OpenAlexW3089934761

What OpenQuestion holds

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Registered trials

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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.