Evidence map›Paper›PMID 41844631›Full record

ArticleNature communications2026

Loss of polarity by Cdc42 depletion and oncogenic Kras activation in the mouse intestinal epithelia leads to a necrotizing enterocolitis (NEC)-like disease.

Zheng Zhang, Cuiqing Fan, Ryan Jorgensen, Pamela Sylvestre, Mike Adam, Yi Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

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

6 authors.

Zheng ZhangDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Cuiqing FanDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0001-9774-9242
Ryan JorgensenDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-7301-4054
Pamela SylvestreDivision of Pathology, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Mike AdamDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0003-4501-4740
Yi ZhengDivision of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. yi.zheng@cchmc.org.ORCID http://orcid.org/0000-0001-7089-6074

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE ARMISTEAD DENSON · 2007 to 2026
$24.4M
Xenotransplant and Genome Editing CoreU54DK126108 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Daniel Starczynowski, YI ZHENG · 2021 to 2026
$5.0M
Novel mechanism of intestinal stem cell agingR01AG063967 · NIA · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2020 to 2024
$2.5M
Rational targeting of Cdc42 to benefit immunotherapyR01CA278756 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Fukun Guo, YI ZHENG · 2024 to 2026
$1.8M
NCI NIH HHS R01 CA278756NIA NIH HHS R01 AG063967NIDDK NIH HHS P30 DK078392NIDDK NIH HHS U54 DK126108
6 · The paper itself

Abstract

Cell polarity is essential for maintaining intestinal epithelial organization and function. Here we show that combined loss of polarity by epithelial loss of Cdc42 with oncogenic Kras expression in mice causes small intestine failure leading to weight loss, inflammation, epithelial necroptosis, and lethality. These phenotypic defects are characterized by a loss of intestinal stem cells, disrupted epithelial architecture, altered hippo signaling, elevated inflammatory cytokines, and activation of necroptotic cell death, that closely resemble necrotizing enterocolitis (NEC). Single-cell transcriptomic analysis reveals a coordinated dysregulation of polarity machinery, inflammatory pathways, and necroptosis program. Suppression of YAP, IL-1, TNFα signaling or necroptosis rescues the intestinal pathology. Similar NEC-like phenotypes arise when Cdc42 loss and oncogenic Kras activation are initiated from intestinal stem cells. These findings provide mechanism insights involving polarity-YAP-IL1/TNFα signaling induced necroptosis for the synergistic effect of hyperactivation of Kras signaling and loss of polarity in disrupting intestinal epithelia.

Indexed as

cdc42 GTP-Binding ProteinCell PolarityEnterocolitis, NecrotizingIntestinal MucosaProto-Oncogene Proteins p21(ras)Adaptor Proteins, Signal TransducingAnimalsFemaleIntestine, SmallMiceMice, Inbred C57BLMice, KnockoutNecroptosisSignal TransductionStem CellsTumor Necrosis Factor-alphaAdaptor Proteins, Signal Transducingcdc42 GTP-Binding ProteinCdc42 protein, mouseHras protein, mouseProto-Oncogene Proteins p21(ras)Tumor Necrosis Factor-alphaYap1 protein, mouseYAP-Signaling Proteins

Identifiers

PMID41844631
PMCPMC13223224

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.