• Connexin 25 (Cx25) is identified as the dominant gap junction protein mediating intercellular Ca2+ communication in human airway basal cell (hBC) clones, essential for maintaining self-renewal and pluripotency.
• Cx25 regulates both in vitro differentiation and in vivo regeneration potential of hBCs in an airway damage model, highlighting its therapeutic relevance for airway repair.
• Abnormal Cx25 expression is observed in respiratory diseases including IPF, COVID-19, and bronchiectasis, suggesting a potential biomarker or therapeutic target.
• The study provides a novel screening method using femtosecond laser-induced Ca2+ waves to identify functional gap junction proteins in stem cell clones.