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

Información del proyecto

SymBreakOrganoid

Identificador del acuerdo de subvención: 758617

DOI

10.3030/758617

Proyecto cerrado

Fecha de la firma de la CE 5 Septiembre 2017

Fecha de inicio 1 Octubre 2018

Fecha de finalización 30 Septiembre 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 500 000,00

Aportación de la UE

€ 1 500 000,00

Coordinado por

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Switzerland

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

Período documentado: 2023-04-01 hasta 2023-09-30

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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

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