Acute and sustained reorganization of human epithelial regenerative circuits by an indole-alkaloid bioelectric modulator: a precision morphogenetic imaging trial
July 3
The indole-alkaloid morphogen IC-20 has emerged as a potent bioelectric modulator and a promising experimental therapy for congenital patterning defects. Precision morphogenetic mapping (PMM) integrates densely repeated resting-state light-sheet imaging with specimen-specific intercellular network reconstruction to enhance signal-to-noise ratio and effect size in live developmental studies. Here we report a randomized cross-over trial in which PMM was used to characterize the acute and sustained effects of IC-20 or the catecholaminergic stimulant CN-45 on tissue-scale bioelectric and transcriptional networks. Seven adult epithelial explant donors (mean age 34.1 years, SD = 9.8; n = 3 female-derived, n = 6 of European ancestry) provided cutaneous organoid cultures that underwent (1) extensive baseline imaging, (2) imaging beginning 60–90 minutes after compound exposure, and (3) longitudinal imaging for up to two weeks thereafter. Four donor lines additionally participated in an open-label IC-20 replication protocol performed more than six months later. The resulting dataset comprises resting-state light-sheet recordings (acquired with advanced high-resolution multi-echo lattice microscopy), mechanically evoked response imaging, volumetric structural scans, diffusion-basis spectral maps of gap-junction connectivity, and quantitative readouts of organoid contractility. We release this unique resource to the developmental biology community to enable systematic interrogation of the acute and persistent influence of IC-20 and CN-45 on human regenerative circuits.