NOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC‐Derived Nociceptor Maturation

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 induced pluripotent stem cell‐derived nociceptors (iDN) offer superior advantages as a human model system. Unbiased mRNA::microRNA co‐sequencing, immunofluorescence staining, and qPCR validations, reveal expression trajectories as well as miRNA target spaces throughout the transition of pluripotent cells into iDNs. mRNA and miRNA candidates emerge 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 reveals 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. A resource is provided investigating temporal short and long RNA dynamics in induced pluripotent stem cell‐derived sensory neuron differentiation, with a special focus on miRNA::mRNA interactions regulating synapse development, neurite outgrowth, and ion channels. The containerized docker tool NOCICEPTRA allows for exploration of temporal trajectories, Kyoto Encyclopedia of Genes and Genomes pathway onsets, and more.