Self-organization and symmetry breaking in intestinal organoid development.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Calcium-Binding Proteins
Cell Cycle Proteins
Intercellular Signaling Peptides and Proteins
/ metabolism
Intestines
/ cytology
Mice
Organoids
/ cytology
Paneth Cells
/ cytology
Phosphoproteins
/ genetics
Receptors, G-Protein-Coupled
/ metabolism
Single-Cell Analysis
YAP-Signaling Proteins
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
22
05
2018
accepted:
27
03
2019
pubmed:
26
4
2019
medline:
10
9
2019
entrez:
26
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31019299
doi: 10.1038/s41586-019-1146-y
pii: 10.1038/s41586-019-1146-y
pmc: PMC6544541
mid: EMS82416
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Calcium-Binding Proteins
0
Cell Cycle Proteins
0
Dlk1 protein, mouse
0
Intercellular Signaling Peptides and Proteins
0
Lgr5 protein, mouse
0
Phosphoproteins
0
Receptors, G-Protein-Coupled
0
YAP-Signaling Proteins
0
Yap1 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66-72Subventions
Organisme : Swiss National Science Foundation
ID : 157531
Pays : Switzerland
Organisme : European Research Council
ID : 758617
Pays : International
Commentaires et corrections
Type : CommentIn
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