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Specialized cytonemes induce self-organization of stem cells

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)7236-7244
Number of pages9
JournalProceedings of National Academy of Sciences USA
Issue number13
Early online date17 Mar 2020
Accepted/In press21 Feb 2020
E-pub ahead of print17 Mar 2020
Published31 Mar 2020


King's Authors


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.

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