Evidence map›Paper›PMID 26040716›Full record

ArticleNature2015

Cloning and variation of ground state intestinal stem cells.

Xia Wang, Yusuke Yamamoto, Lane H Wilson, Ting Zhang, Brooke E Howitt, Melissa A Farrow, Florian Kern, Gang Ning, Yue Hong, Chiea Chuen Khor and 13 more

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing 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

125 citing papers in PubMed.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. International journal of microbiology · 2026
    Article
  4. Article
  5. Article
  6. Novel organoids andParasitology · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Xia WangThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
Yusuke YamamotoThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
Lane H Wilson1] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA [2] Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Ting ZhangGenome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
Brooke E HowittDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02118, USA.
Melissa A FarrowDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Florian KernGenome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
Gang NingThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
Yue HongThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
Chiea Chuen Khor1] Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore [2] Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 119228 Singapore.
Benoit ChevalierThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA.
Denis BertrandGenome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
Lingyan WuGenome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
Niranjan NagarajanGenome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
Francisco A SylvesterDepartment of Pediatrics, Division of Gastroenterology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jeffrey S HyamsDivision of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut 06106, USA.
Thomas DeversDepartment of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Roderick BronsonDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
D Borden LacyDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Khek Yu HoDepartment of Medicine, National University of Singapore, 119228 Singapore.
Christopher P CrumDepartment of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02118, USA.
Frank McKeon1] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA [2] Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore [3] Department of Medicine, National University of Singapore, 119228 Singapore [4] Multiclonal Therapeutics, Inc., Farmington, Connecticut 06032, USA.
Wa Xian1] The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA [2] Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, USA [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02118, USA [4] Department of Medicine, National University of Singapore, 119228 Singapore [5] Multiclonal Therapeutics, Inc., Farmington, Connecticut 06032, USA.

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Structural mechanisms of Clostridium difficile pathogenesisR01AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LACY, DANA BORDEN · 2011 to 2020
$3.9M
Structural Mechanisms of Clostridioides difficile pathogenesisR37AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Dana Borden Lacy · 2021 to 2026
$3.2M
NCI NIH HHS P30 CA034196NIAID NIH HHS AI09575504NIAID NIH HHS R01 AI095755NIAID NIH HHS R37 AI095755
6 · The paper itself

Abstract

Stem cells of the gastrointestinal tract, pancreas, liver and other columnar epithelia collectively resist cloning in their elemental states. Here we demonstrate the cloning and propagation of highly clonogenic, 'ground state' stem cells of the human intestine and colon. We show that derived stem-cell pedigrees sustain limited copy number and sequence variation despite extensive serial passaging and display exquisitely precise, cell-autonomous commitment to epithelial differentiation consistent with their origins along the intestinal tract. This developmentally patterned and epigenetically maintained commitment of stem cells is likely to enforce the functional specificity of the adult intestinal tract. Using clonally derived colonic epithelia, we show that toxins A or B of the enteric pathogen Clostridium difficile recapitulate the salient features of pseudomembranous colitis. The stability of the epigenetic commitment programs of these stem cells, coupled with their unlimited replicative expansion and maintained clonogenicity, suggests certain advantages for their use in disease modelling and regenerative medicine.

Indexed as

Bacterial ToxinsCell DifferentiationCell LineageCells, CulturedClone CellsClostridioides difficileColonEnterocolitis, PseudomembranousEpigenesis, GeneticEpitheliumFetusGenomic InstabilityHumansIntestinesIntestine, SmallOrganoidsBacterial ToxinsClostridium difficile lethal toxin B

Identifiers

PMID26040716
PMCPMC4853906

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.