Evidence map›Paper›PMID 22841781›Full record

ArticleGastroenterology2012

Crypt base columnar stem cells in small intestines of mice are radioresistant.

Guoqiang Hua, Tin Htwe Thin, Regina Feldman, Adriana Haimovitz-Friedman, Hans Clevers, Zvi Fuks, Richard Kolesnick

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
13.0field-weighted citation impact, top 1% 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

134 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.

  1. Pooled it
  2. Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  3. Article
  4. Article
  5. Distinct molecular responses of human intestinal organoids to proton and photon radiation.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis.International journal of molecular sciences · 2024
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

74 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Guoqiang HuaLaboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, New York.
Tin Htwe ThinDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Regina FeldmanDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Adriana Haimovitz-FriedmanDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Hans CleversHubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Zvi FuksDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Richard KolesnickLaboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: r-kolesnick@ski.mskcc.org.
Memorial Sloan Kettering Cancer Center · USUniversity Medical Center Utrecht · NL

Funding

Ceramide synthase as a therapy target in prostate cancerR01CA105125 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI HAIMOVITZ-FRIEDMAN, ADRIANA · 2005 to 2009
$1.6M
NCI NIH HHS R01 CA105125NCI NIH HHS R01#CA105125
6 · The paper itself

Abstract

BACKGROUND &

aimsAdult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that they are highly radiosensitive. Cycling crypt base columnar cells (CBCs) at crypt positions +1-3 recently were defined as an alternative population of ISCs. Little is known about the sensitivity of this stem cell population to radiation.

methodsRadiation-induced lethality of CBCs was quantified kinetically in Lgr5-lacZ transgenic mice. γ-H2AX, BRCA1, RAD51, and DNA-PKcs foci were used as DNA repair surrogates to investigate the inherent ability of CBCs to recognize and repair double-strand breaks. 5-ethynyl-2'-deoxyuridine and 5-bromo-2'-deoxyuridine incorporation assays were used to study patterns of CBC growth arrest and re-initiation of cell cycling. Apoptosis was evaluated by caspase-3 staining.

resultsCBCs are relatively radioresistant, repairing DNA by homologous recombination significantly more efficiently than transit amplifying progenitors or villus cells. CBCs undergo apoptosis less than 24 hours after irradiation (32% ± 2% of total lethality) or mitotic death at 24-48 hours. Survival of CBCs at 2 days predicts crypt regeneration at 3.5 days and lethality from gastrointestinal syndrome. Crypt repopulation originates from CBCs that survive irradiation.

conclusionsAdult ISCs in mice can cycle rapidly yet still be radioresistant. Importantly, homologous recombination can protect adult stem cell populations from genotoxic stress. These findings broaden and refine concepts of the phenotype of adult stem cells.

Indexed as

DNA RepairRadiation ToleranceAdult Stem CellsAnimalsApoptosisBone MarrowCell Cycle CheckpointsDNA Breaks, Double-StrandedJejunumMiceMice, Transgenic

Identifiers

PMID22841781
PMCPMC3480544
OpenAlexW2131815586

What OpenQuestion holds

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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.