Evidence map›Paper›PMID 42575201›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

Tumor Necrosis Factor Receptor 1 Regulates Colonic Mesenchymal Cell Diversity and the Epithelial Stem Cell Niche.

Safina Gadeock, Nandini Girish, Cambrian Y Liu, Ying Huang, Barun Das, Tracy C Grikscheit, D Brent Polk

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Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Safina GadeockDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California.
Nandini GirishDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California.
Cambrian Y LiuDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Medicine, The University of Chicago, Chicago, Illinois.
Ying HuangDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California.
Barun DasDepartment of Pediatrics, University of California San Diego School of Medicine, La Jolla, California.
Tracy C GrikscheitDepartment of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
D Brent PolkDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Rady Children's Hospital, San Diego, San Diego, California. Electronic address: dpolk@ucsd.edu.

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 1990 to 2025
$29.8M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
CYTOKINE REGULATION OF INTESTINAL EPITHELIAL RESTITUTIONR01DK056008 · NIDDK · VANDERBILT UNIVERSITY · PI POLK, D BRENT · 1999 to 2020
$6.8M
Stem Cell Dynamics in Colonic Epithelial RepairR01DK108648 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Cambrian Yangshao Liu, D Brent Polk · 2016 to 2026
$2.7M
Colonic epithelial wound healing by anal transitional cellsR01DK135954 · NIDDK · UNIVERSITY OF CHICAGO · PI Cambrian Yangshao Liu · 2023 to 2026
$2.2M
NIDDK NIH HHS P30 DK042086NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK056008NIDDK NIH HHS R01 DK108648NIDDK NIH HHS R01 DK135954
6 · The paper itself

Abstract

BACKGROUND &

aimsTumor necrosis factor receptor 1 regulates intestinal epithelial survival and repair, yet its role in the colonic mesenchyme remains unclear. We investigated how mesenchymal tumor necrosis factor receptor 1 signaling controls stromal cell identity, stem cell niche function, and epithelial homeostasis.

methodsColonic mesenchymal populations from germline tumor necrosis factor receptor 1-deficient (TNFR1

resultsTumor necrosis factor receptor 1 deletion altered mesenchymal composition, reducing platelet derived growth factor receptor α expression while increasing α smooth muscle actin expression in vivo and in vitro. Single-cell RNA sequencing demonstrated loss of mesenchymal heterogeneity following tumor necrosis factor receptor 1 deletion, including depletion of a distinct tumor necrosis factor- and interferon-responsive mesenchymal subpopulation enriched for Mmp9, Cd200, Traf1, and Tnfrsf9. Transcriptomic profiling revealed downregulation of stem cell niche factors including Rspo3, Wnt2b, and Fgf2, alongside increased extracellular matrix and proliferative signaling pathways, particularly integrin A6, phosphoinositide 3-kinase, mitogen-activated protein kinase, and Ras-associated protein 1 signaling. Mesenchymal tumor necrosis factor receptor 1 deletion impaired epithelial proliferation and reduced Lgr5+ and Ephb3+ intestinal stem cell expression in vivo. In organoid coculture systems, tumor necrosis factor receptor 1-deficient mesenchymal cells suppressed epithelial stem cell marker expression and altered colonoid morphology, effects which were rescued by recombinant R-spondin 3. Integrin A6 blockade restored platelet derived growth factor receptor α and R-spondin 3 expression and normalized proliferative signaling and migration in tumor necrosis factor receptor 1-deficient myofibroblasts. Similarly, tumor necrosis factor receptor 1-dependent regulation of integrin A6, platelet derived growth factor receptor α, and R-spondin 3 was observed in human colonic myofibroblasts.

conclusionsMesenchymal tumor necrosis factor receptor 1 preserves colonic mesenchymal diversity, sustains R-spondin 3-dependent stem cell niche signaling, and maintains intestinal stem cell homeostasis.

Indexed as

IBD OrganoidsMesenchymeStem Cell NicheTNF

Identifiers

PMID42575201
PMCPMC13656958

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.