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Summary: Human pluripotent stem cells (hPSCs) show promise for studying diseases affecting cell populations that are not easily available, including sensory neurons (SNs). Here, we present a differentiation protocol in chemically defined conditions to generate peripheral SNs from hPSCs. We describe four main steps: expansion of hPSCs, neural crest cell (NCC) differentiation, NCC dissociation and replating, and sensory neuron (SN) differentiation. This protocol enables generation of a mechanoreceptor-enriched culture or a population containing all three SN subtypes (nociceptors, mechanoreceptors, and proprioceptors).For complete details on the use and execution of this protocol, please refer to Saito-Diaz et al. (2021).