Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 13, Pages 7236-7244Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1920837117
Keywords
development; cell signaling; tissue formation; cell-cell communication; stem cell
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Funding
- Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre
- King's College London
- King's College Hospital NHS Foundation Trust
- Sir Henry Dale Fellowship [102513/Z/13/Z]
- MRC [MR/R015635/1] Funding Source: UKRI
- Wellcome Trust [102513/Z/13/Z] Funding Source: Wellcome Trust
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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.
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