Evidence map›Paper›PMID 34704277›Full record

ArticleThe EMBO journal2022

Ontogeny and function of the circadian clock in intestinal organoids.

Andrew E Rosselot, Miri Park, Mari Kim, Toru Matsu-Ura, Gang Wu, Danilo E Flores, Krithika R Subramanian, Suengwon Lee, Nambirajan Sundaram, Taylor R Broda and 10 more

Abstract read
In one paragraph

Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

  1. Review
  2. Non-invasiveSurgery open science · 2026
    Article
  3. Expression of gastrointestinal clock genes and associated hormones levels in hibernating and non-hibernating Daurian ground squirrels.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Andrew E RosselotDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Miri ParkDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Mari KimDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Toru Matsu-UraDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0002-9876-3086
Gang WuDivision of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Danilo E FloresDivision of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Krithika R SubramanianDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Suengwon LeeDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Nambirajan SundaramDepartment of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Taylor R BrodaCenter for Stem Cell and Organoid Medicine, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Heather A McCauleyCenter for Stem Cell and Organoid Medicine, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Jennifer A HawkinsDepartment of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kashish ChetalDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nathan SalomonisDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Noah F ShroyerGastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-5934-2852
Michael A HelmrathDepartment of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
James M WellsCenter for Stem Cell and Organoid Medicine, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
John B HogeneschDivision of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Sean R MooreDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID 0000-0003-1150-6632
Christian I HongDepartment of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0001-8618-8128

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Project-3: Modeling EA/TEF in human organoidsP01HD093363 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI Wendy K Chung, Paul scot Kingma · 2017 to 2026
$16.2M
Novel Platforms for Human Intestinal Enteroids: Matrix, Mechanics, and TopographyU19AI116497 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI GRANDE-ALLEN, KATHRYN JANE · 2015 to 2025
$13.2M
Molecular, Cellular and Physiological Mechanisms of the Mammalian Circadian ClockR01NS054794 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HOGENESCH, JOHN B, LIU, ANDREW C. · 2007 to 2022
$8.1M
Organoids as a Model System for Studying Gastrointestinal DiseaseU19AI116491 · NIAID · UNIVERSITY OF CINCINNATI · PI MOORE, SEAN RYAN · 2015 to 2019
$4.6M
Roles of circadian rhythms in gastrointestinal systemsR01DK117005 · NIDDK · UNIVERSITY OF CINCINNATI · PI HONG, CHRISTIAN I · 2018 to 2022
$1.8M
Mechanisms of intestinal stem cell differentiation and plasticity.R01DK118904 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI SHROYER, NOAH FREEMAN · 2018 to 2020
$1.7M
Modeling diabetes using an integrated plate systemUG3DK119982 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE, MOO-YEAL, WELLS, JAMES M · 2018 to 2019
$1.7M
NIAID NIH HHS U19 AI116491NIAID NIH HHS U19 AI116497NICHD NIH HHS P01 HD093363NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK117005NIDDK NIH HHS R01 DK118904NIDDK NIH HHS UG3 DK119982NINDS NIH HHS R01 NS054794
6 · The paper itself

Abstract

Circadian rhythms regulate diverse aspects of gastrointestinal physiology ranging from the composition of microbiota to motility. However, development of the intestinal circadian clock and detailed mechanisms regulating circadian physiology of the intestine remain largely unknown. In this report, we show that both pluripotent stem cell-derived human intestinal organoids engrafted into mice and patient-derived human intestinal enteroids possess circadian rhythms and demonstrate circadian phase-dependent necrotic cell death responses to Clostridium difficile toxin B (TcdB). Intriguingly, mouse and human enteroids demonstrate anti-phasic necrotic cell death responses to TcdB. RNA-Seq analysis shows that ~3-10% of the detectable transcripts are rhythmically expressed in mouse and human enteroids. Remarkably, we observe anti-phasic gene expression of Rac1, a small GTPase directly inactivated by TcdB, between mouse and human enteroids, and disruption of Rac1 abolishes clock-dependent necrotic cell death responses. Our findings uncover robust functions of circadian rhythms regulating clock-controlled genes in both mouse and human enteroids governing organism-specific, circadian phase-dependent necrotic cell death responses, and lay a foundation for human organ- and disease-specific investigation of clock functions using human organoids for translational applications.

Indexed as

Circadian ClocksAnimalsBacterial ProteinsBacterial ToxinsCell DeathCells, CulturedHumansJejunumMiceMice, Inbred C57BLOrganoidsrac1 GTP-Binding ProteinBacterial ProteinsBacterial Toxinsrac1 GTP-Binding ProteinRAC1 protein, humantoxB protein, Clostridium difficilecircadian rhythmsClostridium difficile toxin Bhuman enteroidsintestinal organoidsRac1

Identifiers

PMID34704277
PMCPMC8762567

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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.