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SUMMARY:Organoids and clonal analysis to study cell community interactions
  during pancreas development - Professor Anne Grapin-Botton from DanStem\,
  University of Copenhagen\, Denmark and Max Planck Institute of Molecular 
 Cell Biology and Genetics\, Dresden\, Germany
DTSTART:20181101T140000Z
DTEND:20181101T150000Z
UID:TALK109228@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Pancreas organogenesis relies on the expansion of progenitors 
 and their differentiation into acinar\, ductal and endocrine cells. We hav
 e investigated the contribution of individual progenitors to   organogenes
 is at different times of development using 3-dimensional live imaging\, in
  vivo clonal analysis and single cell transcriptome. Analyses after one di
 vision established the role of symmetric renewing\, symmetric differentiat
 ive and asymmetric divisions\, and revealed stochasticity in endocrine fat
 e commitment (Kim et al.\, PLOS Biology 2015). Analyses over several days 
 addressed cumulative contributions and biases over multiple generations. T
 hese experiments revealed a great deal of heterogeneity in the size of clo
 nes and in the cell types single progenitors generate\, some of which pred
 ictable from their transcriptional state and some reflecting stochastic fa
 te commitment.\n\nTo investigate how single cells exchange information and
  form a community\, we have set-up a method to grow dissociated pancreas p
 rogenitors in 3D. We have observed that small groups but not single cells 
 expand\, differentiate and self-organize in culture to form organoids of t
 housands of cells that reproduce many features of the pancreas (Greggio et
  al.\, Development 2013). We find that heterogeneity in Notch/delta signal
 ing in progenitors is at least in part responsible for the community effec
 t and drives progenitor expansion. The talk will focus on self-organizatio
 n\, especially when and how heterogeneity between cells appears.\n\nFinall
 y\, we will expand on the development of systems to study human developmen
 t at a single-cell resolution\, based on pluripotent stem cells\, human pa
 ncreas organoids and benchmarking to human embryos.
LOCATION:Part II Room\, Department of Genetics\, Downing Site
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