Evidence map›Paper›PMID 36720220›Full record

ArticleImmunity2023

The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Lingjia Kong, Vladislav Pokatayev, Ariel Lefkovith, Grace T Carter, Elizabeth A Creasey, Chirag Krishna, Sathish Subramanian, Bharati Kochar, Orr Ashenberg, Helena Lau and 4 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2023. 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 178 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 2 pooled it
74.5field-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

178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 238 citations in OpenAlex.

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118 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 2 institutions in 1 country.

Lingjia KongBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Vladislav PokatayevBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ariel LefkovithBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Grace T CarterBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Elizabeth A CreaseyCenter for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Chirag KrishnaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sathish SubramanianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Bharati KocharDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Orr AshenbergBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Helena LauBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashwin N AnanthakrishnanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel B GrahamBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Jacques DeguineBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Broad Institute · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Systematic dissection of gut cellular circuits [at single cell resolution]RC2DK114784 · NIDDK · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, GRAHAM, DANIEL BARTHOLOMEW · 2017 to 2021
$9.0M
Opera Phenix high-throughput microplate confocal imager for high-content screeningS10OD026839 · OD · BROAD INSTITUTE, INC. · PI WAGNER, BRIDGET K · 2019 to 2019
$1.0M
NIDDK NIH HHS P30 DK043351NIDDK NIH HHS RC2 DK114784NIH HHS S10 OD026839
6 · The paper itself

Abstract

Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status. Our integrated datasets revealed organ- and compartment-specific responses to acute and chronic inflammation; most immune changes were in cell composition, whereas transcriptional changes dominated among epithelial and stromal cells. These changes correlated with endoscopic inflammation, but small and large intestines exhibited distinct responses, which were particularly apparent when focusing on IBD risk genes. Finally, we mapped markers of disease-associated myofibroblast activation and identified CHMP1A, TBX3, and RNF168 as regulators of fibrotic complications. Altogether, our results provide a roadmap for understanding cell-type- and organ-specific differences in CD and potential directions for therapeutic development.

Indexed as

Crohn DiseaseColonHumansIleumInflammationTranscriptomeUbiquitin-Protein LigasesRNF168 protein, humanUbiquitin-Protein LigasesCrohn's diseasehigh-dimensional profilingIBDinflammationinflammatory bowel diseasemyofibroblastssingle-cell RNA sequencing

Identifiers

PMID36720220
PMCPMC9957882
OpenAlexW4318755347

What OpenQuestion holds

Textmetadata
LicenceTDM
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.