Evidence map›Paper›PMID 31019299›Full record

ArticleNature2019

Self-organization and symmetry breaking in intestinal organoid development.

Denise Serra, Urs Mayr, Andrea Boni, Ilya Lukonin, Markus Rempfler, Ludivine Challet Meylan, Michael B Stadler, Petr Strnad, Panagiotis Papasaikas, Dario Vischi and 3 more

Abstract read
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 304 papers.

0numbers the graph read from it
0cells of the map it votes in
304citing papers in PubMed
33.5field-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

304 citing papers in PubMed, 574 citations in OpenAlex.

  1. Article
  2. Review
  3. Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Denise Serra *Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Urs Mayr *Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Andrea Boni *Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Ilya LukoninFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Markus RempflerFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Ludivine Challet MeylanFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Michael B StadlerFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Petr StrnadFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Panagiotis PapasaikasFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Dario VischiFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Annick WaldtNovartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Guglielmo RomaNovartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
Prisca LiberaliFriedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland. prisca.liberali@fmi.ch.
Friedrich Miescher Institute · CHNovartis (Switzerland) · CHUniversity of Basel · CHÉcole Polytechnique Fédérale de Lausanne · CHSIB Swiss Institute of Bioinformatics · CH

Funding

European Research Council 758617Swiss National Science Foundation 157531
6 · The paper itself

Abstract

Intestinal organoids are complex three-dimensional structures that mimic the cell-type composition and tissue organization of the intestine by recapitulating the self-organizing ability of cell populations derived from a single intestinal stem cell. Crucial in this process is a first symmetry-breaking event, in which only a fraction of identical cells in a symmetrical sphere differentiate into Paneth cells, which generate the stem-cell niche and lead to asymmetric structures such as the crypts and villi. Here we combine single-cell quantitative genomic and imaging approaches to characterize the development of intestinal organoids from single cells. We show that their development follows a regeneration process that is driven by transient activation of the transcriptional regulator YAP1. Cell-to-cell variability in YAP1, emerging in symmetrical spheres, initiates Notch and DLL1 activation, and drives the symmetry-breaking event and formation of the first Paneth cell. Our findings reveal how single cells exposed to a uniform growth-promoting environment have the intrinsic ability to generate emergent, self-organized behaviour that results in the formation of complex multicellular asymmetric structures.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCalcium-Binding ProteinsCell Cycle ProteinsIntercellular Signaling Peptides and ProteinsIntestinesMiceOrganoidsPaneth CellsPhosphoproteinsReceptors, G-Protein-CoupledSingle-Cell AnalysisYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingCalcium-Binding ProteinsCell Cycle ProteinsDlk1 protein, mouseIntercellular Signaling Peptides and ProteinsLgr5 protein, mousePhosphoproteinsReceptors, G-Protein-CoupledYap1 protein, mouseYAP-Signaling Proteins

Identifiers

PMID31019299
PMCPMC6544541
OpenAlexW2941549157

What OpenQuestion holds

Textmetadata
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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.