Implanted flexible electronics reveal principles of human islet cell electrical maturation

• 成果类型: Article
• 署名作者: Li, Qiang; Liu, Ren; Lin, Zuwan; Zhang, Xinhe; Wang, Wenbo; Galicia-Silva, Israeli M.; Liu, Mai; Gao, Zihan; Pollock, Samuel D.; Alvarez-Dominguez, Juan R.; Liu, Jia
• 署名单位: Harvard University; Harvard University; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Howard Hughes Medical Institute; Pennsylvania Medicine
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aeb3295
• 发表日期: 2026-02-19
• 页码: eaeb3295
• 关键词: insulin-secretion; glucose; triggers; potentials; expression; release

摘要

Understanding how human pancreatic alpha and beta cell electrical activities mature is critical for building fully functional stem cell-derived (SC-) pancreatic organoids for research and therapeutics. We implanted tissue-like, stretchable electronics during organogenesis of human pancreatic organoids, enabling months-long, single cell-resolved electrophysiology. Longitudinal single-cell tracking suggested that improved hormone responsiveness reflects increasing activity of SC-alpha and -beta cells with low and high basal firing, linked to induction of energy and hormone metabolism genes. Daily metabolic entrainment showed that circadian hormone secretion rhythms reflect daily oscillation of SC-alpha and -beta electrical characteristics, tied to induction of cell-cell communication and exocytic gene networks, revealing circadian coordination of cell-level, stimulus-coupled responses. Lastly, we showed that electrical stimulation, via implanted actuators, enhances SC-alpha and -beta glucose responsiveness. Our results establish a bioelectronic framework to trace and modulate functional organoid maturation.