Evidence map›Paper›PMID 37883185›Full record

ArticleJCI insight2023

Intestinal transit-amplifying cells require METTL3 for growth factor signaling and cell survival.

Charles H Danan, Kaitlyn E Naughton, Katharina E Hayer, Sangeevan Vellappan, Emily A McMillan, Yusen Zhou, Rina Matsuda, Shaneice K Nettleford, Kay Katada, Louis R Parham and 6 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. HAT1 Regulates Intestinal Stem Cell Proliferation and Differentiation.bioRxiv : the preprint server for biology · 2026
    Article
  5. Marked for Success: How RNA mCellular and molecular gastroenterology and hepatology · 2026
    Review
  6. Review
  7. Targeting of the mNature communications · 2025
    Article
  8. Review
  9. Article
  10. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Charles H DananDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Kaitlyn E NaughtonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Katharina E HayerDepartment of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Sangeevan VellappanWaksman Institute of Microbiology and.
Emily A McMillanDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Yusen ZhouDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Rina MatsudaPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Shaneice K NettlefordDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Kay KatadaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Louis R ParhamDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Xianghui MaDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Afrah ChowdhuryDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Benjamin J WilkinsDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine; University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Premal ShahDepartment of Genetics, Rutgers University, Piscataway, New Jersey, USA.
Matthew D WeitzmanPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kathryn E HamiltonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine.
Children's Hospital of Philadelphia · USRutgers, The State University of New Jersey · USUniversity of Pennsylvania · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
Defining post-transcriptional regulons in intestinal epithelial regenerationR01DK124369 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HAMILTON, KATHRYN ELIZABETH · 2020 to 2024
$2.6M
Functional outcomes of N6-methyladenosine (m6A) recognition by IMP1 during environment induced intestinal stressR21ES031533 · NIEHS · CHILDREN'S HOSP OF PHILADELPHIA · PI HAMILTON, KATHRYN ELIZABETH · 2020 to 2021
$528k
NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK124369NIEHS NIH HHS R21 ES031533
6 · The paper itself

Abstract

Intestinal epithelial transit-amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite these cells' critical roles in intestinal homeostasis and disease, few studies have described genes that are essential to transit-amplifying cell function. We report that RNA methyltransferase-like 3 (METTL3) is required for survival of transit-amplifying cells in the murine small intestine. Transit-amplifying cell death after METTL3 deletion was associated with crypt and villus atrophy, loss of absorptive enterocytes, and uniform wasting and death in METTL3-depleted mice. Sequencing of polysome-bound and methylated RNAs in enteroids and in vivo demonstrated decreased translation of hundreds of methylated transcripts after METTL3 deletion, particularly transcripts involved in growth factor signal transduction such as Kras. Further investigation verified a relationship between METTL3 and Kras methylation and protein levels in vivo. Our study identifies METTL3 as an essential factor supporting the homeostasis of small intestinal tissue via direct maintenance of transit-amplifying cell survival. We highlight the crucial role of RNA modifications in regulating growth factor signaling in the intestine with important implications for both homeostatic tissue renewal and epithelial regeneration.

Indexed as

Proto-Oncogene Proteins p21(ras)Stem CellsAnimalsCell ProliferationCell SurvivalIntercellular Signaling Peptides and ProteinsIntestinesMethyltransferasesMiceRNASignal TransductionIntercellular Signaling Peptides and ProteinsMethyltransferasesMettl3 protein, mouseProto-Oncogene Proteins p21(ras)RNAAdult stem cellsGastroenterologyHomeostasisRNA processing

Identifiers

PMID37883185
PMCPMC10795831
OpenAlexW4387950575

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.