Specialized cytonemes induce self-organization of stem cells

Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7236-7244. doi: 10.1073/pnas.1920837117. Epub 2020 Mar 17.

Abstract

Spatial cellular organization is fundamental for embryogenesis. Remarkably, coculturing embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) recapitulates this process, forming embryo-like structures. However, mechanisms driving ESC-TSC interaction remain elusive. We describe specialized ESC-generated cytonemes that react to TSC-secreted Wnts. Cytoneme formation and length are controlled by actin, intracellular calcium stores, and components of the Wnt pathway. ESC cytonemes select self-renewal-promoting Wnts via crosstalk between Wnt receptors, activation of ionotropic glutamate receptors (iGluRs), and localized calcium transients. This crosstalk orchestrates Wnt signaling, ESC polarization, ESC-TSC pairing, and consequently synthetic embryogenesis. Our results uncover ESC-TSC contact-mediated signaling, reminiscent of the glutamatergic neuronal synapse, inducing spatial self-organization and embryonic cell specification.

Keywords: cell signaling; cell–cell communication; development; stem cell; tissue formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / physiology*
  • Cell Differentiation
  • Cell Line
  • Drosophila
  • Embryo, Mammalian / metabolism
  • Embryonic Development / physiology
  • Embryonic Stem Cells / metabolism*
  • Mice
  • Pseudopodia / metabolism*
  • Trophoblasts / metabolism
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / physiology

Substances

  • Wnt Proteins