A single-cell investigation of cell heterogeneity and its role as a driver of pancreas and pancreatic organoid formation

Date

Jan 24, 2017

Time

11:00 AM - 12:00 PM

Speaker

Anne Grapin-Botton

Affiliation

University of Copenhagen, Denmark

Language

en

Main Topic

Biologie

Other Topics

Biologie

Host

Elisabeth Knust

Description

Pancreas organogenesis relies on the expansion of progenitors and their differentiation into acinar, ductal and endocrine cells. We have investigated the contribution of individual progenitors to organogenesis at different times of development using 3-dimensional live imaging and in vivo clonal analysis. Analyses after one division establish the role of symmetric renewing, symmetric differentiative and asymmetric divisions, and reveal stochasticity in endocrine fate commitment (Kim et al., PLOS Biology 2015). Analyses over several days address cumulative contributions and biases over multiple generations. These experiments reveal a great deal of heterogeneity in the size of clones and in the cell types single progenitors generate. We will discuss whether this is caused by molecular heterogeneity in the progenitor population, as analyzed by tracking specific populations and comparing with single cell expression data, or whether it reflects stochastic fate commitment. To investigate how single cells exchange information and form a community, we have set-up a method to grow dissociated pancreas progenitors in 3D. We have observed that small groups but not single cells expand, differentiate and self-organize in culture to form organoids of thousands of cells that reproduce many features of the pancreas (Greggio et al., Development 2013). We find that heterogeneity in Notch/delta signaling in progenitors is at least in part responsible for the community effect and drives progenitor expansion. The talk will focus on self-organization, especially when and how heterogeneity between cells appears.

Last modified: Jan 25, 2017, 8:57:31 AM