Presented By: LSA Biophysics
Professor Eric D. Siggia - The Rockefeller University
"Exploring embryonic patterning with colonies of human embryonic stem cells"
Abstract: Stem cells are commonly grown on surfaces and when induced to differentiate show disorganized arrangements of fates. The simple process of spatial confinement and BMP4 or Wnt induction leads to a reproducible arrangement of extraembryonic and germ layer fates as a function of colony radius that mimics the proximal distal axis in the mammalian embryo. Fate is defined by distance from the colony boundary which can be hundreds of microns away. The stem cell colonies also form a radially localized primitive streak and exhibit gastrulation like movements. We have characterized the molecular events that control our radial patterns, which include receptor occlusion in apical-basal polarized colonies, and the production and diffusion of secreted inhibitors and secondary morphogens. Three dimensional culture, creates closed epithelia shell that resemble the postimplantation epiblast. They will spontaneously symmetry break into a primitive streak and a region resembling the anterior epiblast. This quantitative assay shows in a context very different from the embryo how the canonical signaling pathways, generate spatial patterns over large scales, but it also reveals cell biological aspects of signaling that are difficult to study in mammalian embryos.
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