Back
Full-text
Journal article

Self-organization and symmetry breaking in intestinal organoid development.

  • Serra D Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Mayr U Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Boni A Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Lukonin I Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Rempfler M Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Challet Meylan L Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Stadler MB Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Strnad P Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Papasaikas P Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Vischi D Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
  • Waldt A Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
  • Roma G Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
  • Liberali P Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland. prisca.liberali@fmi.ch.
Show more…
  • 2019-04-26
Published in:
  • Nature. - 2019
Adaptor Proteins, Signal Transducing
Animals
Calcium-Binding Proteins
Cell Cycle Proteins
Intercellular Signaling Peptides and Proteins
Intestines
Mice
Organoids
Paneth Cells
Phosphoproteins
Receptors, G-Protein-Coupled
Single-Cell Analysis
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/17874
Statistics
Document views: 27 File downloads:
  • fulltext.pdf: 0