NOCICEPTRA: Gene and microRNA signatures and their trajectories characterizing human iPSC-derived nociceptor maturation

Abstract

Nociceptors are primary afferent neurons serving the reception of acute pain but also the transit into maladaptive pain disorders. Since native human nociceptors are hardly available for mechanistic functional research, and rodent models do not necessarily mirror human pathologies in all aspects, human iPSC-derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co-sequencing, immunofluorescence staining and qPCR validations, revealed expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs. mRNA and miRNA candidates emerged as regulatory hubs for neurite outgrowth, synapse development and ion channel expression. The exploratory data analysis tool NOCICEPTRA is provided as a containerized platform to retrieve experimentally determined expression trajectories, and to query custom gene sets for pathway and disease enrichments. Querying NOCICEPTRA for marker genes of cortical neurogenesis revealed distinct similarities and differences for cortical and peripheral neurons. The platform provides a public domain neuroresource to exploit the entire data sets and explore miRNA and mRNA as hubs regulating human nociceptor differentiation and function.

Single cell, whole embryo phenotyping of pleiotropic disorders of mammalian development

“…10e ). As such, the apparently unique signature of Scn11a GOF cells might be attributable to these embryos simply being earlier in development, suggesting a more global role for sodium ion channels not only for neuronal function but also early development and cell fate determination 64 . Incorrect staging is formally possible, but unlikely because the embryos derived from three independent litters.…”