Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration
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, spatiotemp...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224008228 |
| _version_ | 1797202989115506688 |
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| author | Jonathan D. Louie Camila M. Barrios-Camacho Benjamin H. Bromberg Constantin A. Hintschich James E. Schwob |
| author_facet | Jonathan D. Louie Camila M. Barrios-Camacho Benjamin H. Bromberg Constantin A. Hintschich James E. Schwob |
| author_sort | Jonathan D. Louie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T08:12:12Z |
| format | Article |
| id | doaj.art-c78ee9f9e05e49d38bfbedb23cb9506c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T08:12:12Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c78ee9f9e05e49d38bfbedb23cb9506c2024-04-17T04:49:45ZengElsevieriScience2589-00422024-05-01275109600Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regenerationJonathan D. Louie0Camila M. Barrios-Camacho1Benjamin H. Bromberg2Constantin A. Hintschich3James E. Schwob4Medical 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, USANeuroscience 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, USADepartment of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USADepartment 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, USADepartment of Developmental, Molecular & Chemical Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA 02111, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224008228sensory neurosciencecell biologyOmics |
| spellingShingle | Jonathan D. Louie Camila M. Barrios-Camacho Benjamin H. Bromberg Constantin A. Hintschich James E. Schwob Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration iScience sensory neuroscience cell biology Omics |
| title | Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration |
| title_full | Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration |
| title_fullStr | Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration |
| title_full_unstemmed | Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration |
| title_short | Spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro-neurogenic pathway during injury-induced olfactory epithelium regeneration |
| title_sort | spatiotemporal dynamics exhibited by horizontal basal cells reveal a pro neurogenic pathway during injury induced olfactory epithelium regeneration |
| topic | sensory neuroscience cell biology Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224008228 |
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