Derivation and analysis of human somatic sensory neuron subtypes facilitated through fluorescent hPSC reporters

Peripheral sensory neuropathy (PSN) is associated with several devastating neurological conditions, yet effective strategies to prevent or alleviate the consequences of PSN are nearly non-existent. A major challenge in the development of better therapeutic interventions is the lack of appropriate human model systems. Human induced pluripotent stem cell (hiPSC)-derived somatosensory neurons present a promising strategy to overcome this issue but remain of limited translational utility, in part due to the low efficiency and lack of sensory subtype selectivity of the existing sensory neuron derivation protocols. To improve upon iPSC-based somatosensory disease models, we here describe the generation and validation of a genetic toolset to fluorescently label all or distinct (nociceptor, low threshold mechanoreceptor, and proprioceptor) somatosensory subtypes. These new resources will be transformative for hPSC-based approaches in PSN disease modeling-a critical step toward translating new findings into clinically relevant therapeutic strategies.