Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.

Autonomic parasympathetic neurons (parasymNs) control unconscious body responses, including "rest-and-digest." ParasymN innervation is important for organ development, and parasymN dysfunction is a hallmark of autonomic neuropathy. However, parasymN function and dysfunction in humans are vastly understudied due to the lack of a model system. Human pluripotent stem cell (hPSC)-derived neurons can fill this void as a versatile platform. Here, we developed a differentiation paradigm detailing the derivation of functional human parasymNs from Schwann cell progenitors. We employ these neurons (1) to assess human autonomic nervous system (ANS) development, (2) to model neuropathy in the genetic disorder familial dysautonomia (FD), (3) to show parasymN dysfunction during SARS-CoV-2 infection, (4) to model the autoimmune disease Sjögren's syndrome (SS), and (5) to show that parasymNs innervate white adipocytes (WATs) during development and promote WAT maturation. Our model system could become instrumental for future disease modeling and drug discovery studies, as well as for human developmental studies.

Involvement of different mesotocin (oxytocin homologue) populations in sexual and aggressive behaviours of the brown anole.

The oxytocin (OT) family of neuropeptides are known to modulate social behaviours and anxiety in mammals and birds. We investigated cell numbers and neural activity, assessed as Fos induction, within magnocellular and parvocellular populations of neurons producing the OT homologue mesotocin (MT, Ile(8)-oxytocin). This was conducted within the male brown anole lizard, Anolis sagrei, following agonistic or courtship encounters with a conspecific. Both neurons colocalizing and not colocalizing corticotropin-releasing factor (CRF) were examined. Parvocellular neurons of the paraventricular nucleus exhibited a positive correlation between courtship frequency and Fos colocalization, regardless of whether they produce just MT or MT + CRF. Magnocellular populations showed only trends towards positive relationships with courtship and no cell populations showed aggression-related Fos induction. These findings are novel because they demonstrate the involvement of MT neurons in male social behaviour, especially in reptiles for whom the involvement of MT in social behaviour was previously unknown.