세미나

Touch, pain, itch, and temperature – the fundamental sensory experiences of everyday life – emerge from the dynamic interaction between the skin and its innervating sensory neurons. Reconstituting this cellular diversity and functional sensory integration in a human-specific in vitro system has remained a major challenge. Human skin organoids (SkOs) derived from pluripotent stem cells recapitulate key features of fetal skin development, including stratified epidermis, dermis, appendage formation, and intrinsic multilineage organization, providing a platform to investigate how diverse cell types emerge, self-organize, and interact during skin development. To establish a pain-sensing skin organoid (painSkO), pre-differentiated sensory neural progenitors were incorporated into SkOs through two complementary approaches: floating assembloid cultures and a microfluidic SkO-on-chip system. In both platforms, neural progenitors migrated into and integrated within the organoid, differentiated into PRPH⁺ sensory neurons, and formed dorsal root ganglion-like structures with axonal projections innervating skin compartments, including hair follicles. Capsaicin-induced calcium transients in GCaMP-labeled neurons confirmed functional nociceptor activity, and mechanical stimulation further demonstrated stimulus-responsive neural activity, supporting the emergence of functional sensory units within engineered human skin tissue. Together, these SkO-based systems establish a physiologically relevant platform to study skinneuro interactions and complex cell-cell communication, enabling the investigation of human sensory biology at the tissue level.