In vitro programming and pseudounipolarization of human iPSC-derived sensory neurons

Abstract

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.

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BibTeX

@misc{roderer2026vitro,
  title = {{In vitro programming and pseudounipolarization of human iPSC-derived sensory neurons}},
  author = {P. Röderer and A. C. Costa and M. Lürkens and F. M. Roll and F. Buck and L. Heidrich and J. Aicher and A. Neureiter and O. Mossad and H. Trucks-Jansen and K. Le Cann and A. K. Kalia and R. Balaji and V. Arndt and A. Zellner and Y. Mecdad and T. Bajaj and M. Stüger and M. K. Schwarz and A. Nitzsche and N. C. Gassen and N. Haag and M. Schröter and A. Lampert and M. M. Sousa and O. Brüstle},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.18.747563},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.18.747563v1},
  note = {CC BY-NC},
}

RIS

TY  - UNPB
TI  - In vitro programming and pseudounipolarization of human iPSC-derived sensory neurons
AU  - P. Röderer
AU  - A. C. Costa
AU  - M. Lürkens
AU  - F. M. Roll
AU  - F. Buck
AU  - L. Heidrich
AU  - J. Aicher
AU  - A. Neureiter
AU  - O. Mossad
AU  - H. Trucks-Jansen
AU  - K. Le Cann
AU  - A. K. Kalia
AU  - R. Balaji
AU  - V. Arndt
AU  - A. Zellner
AU  - Y. Mecdad
AU  - T. Bajaj
AU  - M. Stüger
AU  - M. K. Schwarz
AU  - A. Nitzsche
AU  - N. C. Gassen
AU  - N. Haag
AU  - M. Schröter
AU  - A. Lampert
AU  - M. M. Sousa
AU  - O. Brüstle
PY  - 2026
DA  - 2026/09/18
PB  - bioRxiv
DO  - 10.64898/2026.09.18.747563
UR  - https://www.biorxiv.org/content/10.64898/2026.09.18.747563v1
AB  - 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.
ER  -

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