The mechanisms underlying touch sensation in humans are poorly understood. Here, the authors induced human stem-cell-derived neural crest cells in vitro to produce neurons that morphologically and electrophysiologically resembled a subset of low-threshold mechanoreceptors (LTMRs), which convey touch. Deletion of the gene encoding PIEZO2, an ion channel activated by mechanical stimuli, from human embryonic stem cells rendered the subsequently induced LTMRs mechano-insensitive, indicating that this channel is required for mechanotransduction in these LTMRs.