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Papers of the Week

Papers: 8 Apr 2023 - 14 Apr 2023

Basic Science, Methodology, Resource

In Vitro Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

2023 Apr 11

Stem Cell Reports




Scalable generation of sensory neurons from human pluripotent stem cells.


Deng T, Jovanovic VM, Tristan CA, Weber C, Chu PH, Inman J, Ryu S, Jethmalani Y, Ferreira de Sousa J, Ormanoglu P, Twumasi P, Sen C, Shim J, Jayakar S, Bear Zhang HX, Jo S, Yu W, Voss TC, Simeonov A, Bean BP, Woolf CJ, Singeç I


Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10 neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NA1.7, NA1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.