Cell-to-cell variability during symmetry breaking in organoid development

Informations projet

SymBreakOrganoid

N° de convention de subvention: 758617

DOI

10.3030/758617

Projet clôturé

Date de signature de la CE 5 Septembre 2017

Date de début 1 Octobre 2018

Date de fin 30 Septembre 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 500 000,00

Contribution de l’UE

€ 1 500 000,00

Coordonné par

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Switzerland

Periodic Reporting for period 4 - SymBreakOrganoid (Cell-to-cell variability during symmetry breaking in organoid development)

Période du rapport: 2023-04-01 au 2023-09-30

Résumé du contexte et des objectifs généraux du projet

The overall objectives of the project are to determine the cause and consequences of cellular heterogeneity in intestinal organoids. We have established novel experimental frameworks for analyzing collective behaviors of cells in tissue and develop perturbation methods to have improved spatio temporal resolution. This is allowing us to understand design principles of tissue development, homeostasis and regeneration. We are also developed tools to perturb individual cells and create synthetic heterogeneities in tissues. This then allowed us to translate some of our finding in human organoids and discover novel mechanisms of human intestinal regeneration.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

For the grant we performed imaging multiplexed time course experiments of organoid development for determining the source of cell to cell variability and to predict symmetry breaking events. We then performed scRNAseq and ATACseq time course experiment to understand the extend of cell to cell variability. Finally, we built a light sheet microscope that allows us to follow the formation of organoids from one cell to a fully formed organoid to follow the consequence of cellular heterogeneity. We have implementing the optogenetic perturbations in the light sheet to control cellular heterogeneity.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The work establishes novel paradigm on how to analyzer collective behaviors. We also discovered that organoid development follow a regenerative response and this is having incredible implication in how to study regeneration in vitro, in mouse but also in human. It allowed us to test novel compounds in intestinal regeneration in vivo. Finally, it allowed us to set the standard in the field on how to perform image based analysis in organoids

picture.jpg