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, Annick Waldt, Guglielmo Roma and Prisca Liberali ()
Additional contact information
Denise Serra: Friedrich Miescher Institute for Biomedical Research (FMI)
Urs Mayr: Friedrich Miescher Institute for Biomedical Research (FMI)
Andrea Boni: Friedrich Miescher Institute for Biomedical Research (FMI)
Ilya Lukonin: Friedrich Miescher Institute for Biomedical Research (FMI)
Markus Rempfler: Friedrich Miescher Institute for Biomedical Research (FMI)
Ludivine Challet Meylan: Friedrich Miescher Institute for Biomedical Research (FMI)
Michael B. Stadler: Friedrich Miescher Institute for Biomedical Research (FMI)
Petr Strnad: Friedrich Miescher Institute for Biomedical Research (FMI)
Panagiotis Papasaikas: Friedrich Miescher Institute for Biomedical Research (FMI)
Dario Vischi: Friedrich Miescher Institute for Biomedical Research (FMI)
Annick Waldt: Novartis Pharma AG
Guglielmo Roma: Novartis Pharma AG
Prisca Liberali: Friedrich Miescher Institute for Biomedical Research (FMI)

Nature, 2019, vol. 569, issue 7754, 66-72

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (10)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1146-y Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:569:y:2019:i:7754:d:10.1038_s41586-019-1146-y

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1146-y

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().