Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration.
iScience
; 27(5): 109600, 2024 May 17.
Article
en En
| MEDLINE
| ID: mdl-38650985
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos