Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration
Jonathan D. Louie,
Camila M. Barrios-Camacho,
Benjamin H. Bromberg,
Constantin A. Hintschich,
James E. Schwob
Affiliations
Jonathan D. Louie
Medical Scientist Training Program, Tufts University School of Medicine, Boston, MA 02111, USA; Neuroscience Graduate Program, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Department of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA
Camila M. Barrios-Camacho
Neuroscience Graduate Program, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Department of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA
Benjamin H. Bromberg
Department of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA
Constantin A. Hintschich
Department of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Department of Otorhinolaryngology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany; Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA
James E. Schwob
Department of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Corresponding author
Summary: 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.
