Open AccessNOCICEPTRA: Gene and microRNA Signatures and Their Trajectories Characterizing Human iPSC‐Derived Nociceptor Maturation
Author(s) -
Zeidler Maximilian,
Kummer Kai K.,
Schöpf Clemens L.,
Kalpachidou Theodora,
Kern Georg,
Cader M. Zameel,
Kress Michaela
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202102354
Subject(s) - nociceptor , microrna , induced pluripotent stem cell , neuroscience , neurogenesis , neurite , biology , computational biology , microbiology and biotechnology , gene , nociception , genetics , receptor , embryonic stem cell , in vitro
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.