Year: 2026
Type: preprint
Abstract: Summary Ectopic expression of NGN1 , BRN3A and ISLET1 (NBI) from a safe harbor locus in induced pluripotent stem cells (iPSCs) yielded robust differentiation into functional sensory neurons (iNBI-SNs) within seven days. Single nucleus transcriptomics identified peripheral sensory neuron profiles of nociceptors and mechanoreceptors. Electrophysiological studies showed that more than 98 % of iNBI-SNs display TTX-resistant sodium currents and that they establish functional connections to excitatory CNS neurons. iNBI-SNs derived from patients with inherited erythromelalgia, a pain disorder associated with gain-of-function mutations in the Nav1.7 sodium channel showed pathologically increased firing rates which could be partially rescued with a Nav1.7 inhibitor. Notably, iNBI-SNs acquire a characteristic pseudounipolar morphology upon co-culture with embryonic rodent DRG cells. Taken together, NBI-based forward programming of iPSCs represents a robust approach for the generation of human sensory neurons suitable for developmental, disease- and therapy-related studies.
Authors: Pascal Röderer, Ana Catarina Costa, Martha Lürkens, Fiona Maria Roll, Franziska Buck, Luzia Heidrich, Jasmin Aicher, Anika Neureiter, Omar Mossad, Holger Trucks-Jansen, Kim Le Cann, Anil Kumar Kalia, Ramya Balaji, Verena Arndt, Andreas Zellner, Yara Mecdad, Thomas Bajaj, Martin Stüger, Martin Karl Schwarz, Anja Nitzsche, Nils Christian Gassen, Natja Haag, Manuel Schröter, Angelika Lampert, Monica M Sousa, Oliver Brüstle
Institutions: University of Bonn, University Hospital Bonn, Universitätsklinikum Aachen, Life & Brain (Germany), RWTH Aachen University, Universidade do Porto, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Instituto de Biologia Molecular e Celular, Grünenthal Group (Germany), ETH Zurich
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213951594