Authors: Chase R, de la Peña JB, Smith PR, Lawson J, Lou TF, Stanowick AD, Black BJ, Campbell ZT.
The FASEB Journal, 2022.
Scientists use Axion’s Maestro platform and other methods to explore mRNA expression in hiPSC sensory neurons and identify a potential therapeutic target for inflammatory pain.
Human induced pluripotent stem cell (hiPSC) models are transforming the study of pain and therapeutic discovery, but the impact of different tissue microenvironments on mRNA expression is not fully understood. In this study, scientists use a multiplatform approach including high-throughput sequencing to compare gene expression and downstream effects in mature hiPSC sensory neurons cultured in isolation and neural co-cultures generated with hiPSC astrocytes, using undifferentiated hiPSCs and mouse dorsal root ganglia as controls.
To measure spontaneous extracellular action potentials in the hiPSC sensory monocultures and co-cultures in vitro, the team used Axion’s label-free, noninvasive Maestro platform. Overall findings demonstrated that hiPSC sensory neuron models express many key markers linked to pain and that the addition of astrocytes promotes neuronal maturation as demonstrated by expression of DRG enriched transcripts. The researchers also identified the eIF5A protein as a potential drug target for inflammatory pain. In sum, the authors suggest that hiPSC models “are a powerful tool for modeling patient mutations and human neuronal physiology,” and provide a promising platform for the discovery of new pain therapies that act directly on nociceptors