Specialized cytonemes induce self-organization of stem cells

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 ES...

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Detalles Bibliográficos
Autores principales: Junyent, Sergi, Garcin, Clare L., Szczerkowski, James L. A., Trieu, Tung-Jui, Reeves, Joshua, Habib, Shukry J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132109/
https://www.ncbi.nlm.nih.gov/pubmed/32184326
http://dx.doi.org/10.1073/pnas.1920837117
Descripción
Sumario: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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