Abstract
Spatial cellular organization is fundamental for embryogenesis. Remarkably, coculturing embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) recapitulates this process, forming embryolike 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 selforganization and embryonic cell specification.
| Original language | English |
|---|---|
| Pages (from-to) | 7236-7244 |
| Number of pages | 9 |
| Journal | Proceedings of National Academy of Sciences USA |
| Volume | 117 |
| Issue number | 13 |
| Early online date | 17 Mar 2020 |
| DOIs | |
| Publication status | Published - 31 Mar 2020 |
Keywords
- Cell signaling
- Cell-cell communication
- Development
- Stem cell
- Tissue formation