ArticlebioRxiv : the preprint server for biology2025
Induction of Human Pruriceptors from Pluripotent Stem Cells via Transcription Factors.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Pruriception is crucial for defense against external stimuli but can lead to chronic pruritus, a debilitating condition affecting millions worldwide. Our understanding of the cellular and molecular mechanisms behind the sensation of itch has been hindered by the lack of functional human models. Here, we address this limitation by developing a protocol to generate induced pruriceptors (iPruriceptors) from human pluripotent stem cells (hPSCs). We compared two differentiation approaches: a direct method via forced expression of transcription factors (TFs) in hPSCs, and a 2-step process through expression of TFs in hPSC-derived neural crest cells (NCCs). The 2-step protocol proved superior in inducing a transcriptional program that closely resembles that of human pruriceptors. Our optimized protocol employs forced expression of NGN1 and ISL1 to drive differentiation from NCCs into pruriceptors, enhancing the expression of known pruritogen receptors such as IL31RA, which pairs with OSMR, and HRH1. The induction of this transcriptional program leads to functional maturation of iPruriceptors. Accordingly, iPruriceptors exhibit robust responses to itch stimuli and
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