TY - JOUR
T1 - Specialized cytonemes induce self-organization of stem cells
AU - Junyent, Sergi
AU - Garcin, Clare L.
AU - Szczerkowski, Jamie L. A.
AU - Trieu, Tung-Jui
AU - Reeves, Joshua
AU - Habib, Shukry J.
PY - 2020/3/31
Y1 - 2020/3/31
N2 - 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.
AB - 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.
KW - Cell signaling
KW - Cell-cell communication
KW - Development
KW - Stem cell
KW - Tissue formation
UR - http://www.scopus.com/inward/record.url?scp=85082753651&partnerID=8YFLogxK
U2 - 10.1073/pnas.1920837117
DO - 10.1073/pnas.1920837117
M3 - Article
SN - 0027-8424
VL - 117
SP - 7236
EP - 7244
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -