Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration

Louie, Jonathan D. and Barrios-Camacho, Camila M. and Bromberg, Benjamin H. and Hintschich, Constantin A. and Schwob, James E. (2024) Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration. ISCIENCE, 27 (5): 109600. ISSN 2589-0042

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Abstract

Horizontal basal cells (HBCs) mediate olfactory epithelium (OE) regeneration following severe tissue injury. The dynamism of the post -injury environment is well illustrated by in silico modeling of RNA sequencing data that demonstrate an evolving HBC transcriptome. Unfortunately, spatiotemporally dynamic processes occurring within HBCs in situ remain poorly understood. Here, we show that HBCs at 24 h post -OE injury spatially redistribute a constellation of proteins, which, in turn, helped to nominate Rac1 as a regulator of HBC differentiation during OE regeneration. Using our primary culture model to activate HBCs pharmacologically, we demonstrate that concurrent Rac1 inhibition attenuates HBC differentiation potential. This in vitro functional impairment manifested in vivo as decreased HBC differentiation into olfactory sensory neurons following HBC-specific Rac1 conditional knockout. Taken together, our data potentiate the design of hyposmia-alleviating therapies and highlight aspects of in situ HBC spatiotemporal dynamics that deserve further investigation.

Item Type: Article
Uncontrolled Keywords: N-TERMINAL KINASE; C-JUN; STEM-CELLS; EXTRACELLULAR-MATRIX; SUSTENTACULAR CELLS; PROTEIN-KINASE; KAPPA-B; RAC1; ACTIVATION; INTEGRIN
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Jan 2026 09:21
Last Modified: 14 Jan 2026 09:21
URI: https://pred.uni-regensburg.de/id/eprint/65072

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