Evidence map›Paper›PMID 27237597›Full record

ArticleGastroenterology2016

Mouse Label-Retaining Cells Are Molecularly and Functionally Distinct From Reserve Intestinal Stem Cells.

Ning Li, Angela Nakauka-Ddamba, John Tobias, Shane T Jensen, Christopher J Lengner

Abstract read
In one paragraph

Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing 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

64 citing papers in PubMed.

  1. Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  2. Metrnl in mitigating radiation enteritisActa pharmaceutica Sinica. B · 2026
    Article
  3. Fasting primes small intestinal regeneration after damage via a microbiome-metabolite-chromatin axis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
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  9. Dietary and metabolic effects on intestinal stem cells in health and disease.Nature reviews. Gastroenterology & hepatology · 2025
    Review
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Ning LiDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Angela Nakauka-DdambaDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
John TobiasPenn Genomic Analysis Core, University of Pennsylvania, Philadelphia, Pennsylvania.
Shane T JensenDepartment of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania.
Christopher J LengnerDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Cell and Developmental Biology, Perelman School of Medicine, School of Medicine, and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Lengner@vet.upenn.edu.

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5M
Deregulation of MSI RNA-binding proteins promotes intestinal tumorigenesisR01CA168654 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LENGNER, CHRISTOPHER JOACHIM · 2012 to 2021
$3.7M
The basis for and function of enteroendocrine lineage plasticity in the intestinal DNA damage responseR01DK106309 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LENGNER, CHRISTOPHER JOACHIM · 2016 to 2023
$3.3M
NCI NIH HHS R01 CA168654NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK106309
6 · The paper itself

Abstract

BACKGROUND &

aimsIntestinal homeostasis and regeneration after injury are controlled by 2 different types of cells: slow cycling, injury-resistant reserve intestinal stem cells (ISCs) and actively proliferative ISCs. Putative reserve ISCs have been identified using a variety of methods, including CreER insertions at Hopx or Bmi1 loci in mice and DNA label retention. Label-retaining cells (LRCs) include dormant stem cells in several tissues; in the intestine, LRCs appear to share some properties with reserve ISCs, which can be marked by reporter alleles. We investigated the relationships between these populations.

methodsStudies were performed in Lgr5-EGFP-IRESCreERT2, Bmi1-CreERT2, Hopx-CreERT2, and TRE-H2BGFP::Hopx-CreERT2::lox-stop-lox-tdTomato mice. Intestinal epithelial cell populations were purified; we compared reporter allele-marked reserve ISCs and several LRC populations (marked by H2B-GFP retention) using histologic flow cytometry and functional and single-cell gene expression assays.

resultsLRCs were dynamic and their cellular composition changed with time. Short-term LRCs had properties of secretory progenitor cells undergoing commitment to the Paneth or enteroendocrine lineages, while retaining some stem cell activity. Long-term LRCs lost stem cell activity and were a homogenous population of terminally differentiated Paneth cells. Reserve ISCs marked with HopxCreER were primarily quiescent (in G0), with inactive Wnt signaling and robust stem cell activity. In contrast, most LRCs were in G1 arrest and expressed genes that are regulated by the Wnt pathway or are in the secretory lineage.

conclusionsLRCs are molecularly and functionally distinct from reporter-marked reserve ISCs. This information provides an important basis for future studies of relationships among ISC populations.

Indexed as

Cell DifferentiationAnimalsFlow CytometryGene ExpressionIntestinesMiceStem CellsCryptDifferentiationEpitheliumQuiescence

Identifiers

PMID27237597
PMCPMC4961601

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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.