Abstract: Parasympathetic neurons (parasymN) are important for unconscious body responses, including rest-and-digest and calming the body. Disclosed herein is a chemically defined differentiation protocol that generates parasympathetic neurons from stem cells. The protocol yields high efficiency and purity cultures that are electrically active and respond to specific stimuli. Their molecular characteristics and maturation stage are described and evidence for their use as a model for studying parasymN function and dysfunction. Cell populations and compositions formed from the resulting cells, as well as methods of their use for disease treatment, drug screening, and modeling of human disorders affecting parasymN are also provided.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).

Abstract: The three main peripheral sensory neuron (SN) subtypes, nociceptors, mechanoreceptors, and proprioceptors localize to dorsal root ganglia (DRG) and convey sensations such as pain, temperature, pressure and limb movement/position. Disclosed herein is a chemically defined differentiation protocol that generates all three SN subtypes from the same starting population, as well as methods to enrich for each individual subtypes. The protocol yields high efficiency and purity cultures that are electrically active and respond to specific stimuli. Their molecular character and maturity stage are described and evidence for their use as an axotomy model is exemplified. Cell populations and compositions formed from the resulting cells, as well as methods of their use for disease treatment, drug screening, and modeling of human disorders affecting SNs are also provided.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells (e.g., human stem cells) into proprioceptors, proprioceptors generated by such methods, and compositions comprising such proprioceptors. The presently disclosed subject matter also provides for uses of such proprioceptors for preventing and/or treating disorders of proprioceptor neurons and/or neurodegenerative disorders (e.g., Friedreich's Ataxia).