G2 Stem Cells Orchestrate Time-Directed, Long-Range Coordination of Calcium Signaling During Skin Epidermal Regeneration

The study explored how epidermal stem cells coordinate calcium (Ca2+) signaling during skin regeneration, using advanced imaging and a machine learning tool called Geometric Scattering Trajectory Homology (GSTH). It was found that stem cells exhibit dynamic intercellular Ca2+ signaling across neighborhoods of up to 10 cells, coordinated over time among thousands of cells. This coordination was identified as an emergent property of the stem cell compartment, distinct from neuronal tissues. G2 phase stem cells were shown to govern these signaling patterns, with Connexin43 (Cx43) playing a crucial role in mediating connectivity between local signaling neighborhoods. The research provided insights into the communication mechanisms of stem cells at different cell cycle stages, highlighting the importance of phase diversity for effective tissue-wide communication during epidermal regeneration.