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An in vitro model of acute horizontal basal cell activation reveals gene regulatory networks underlying the nascent activation phase.
- Source :
-
Stem cell reports [Stem Cell Reports] 2024 Aug 13; Vol. 19 (8), pp. 1156-1171. Date of Electronic Publication: 2024 Jul 25. - Publication Year :
- 2024
-
Abstract
- While horizontal basal cells (HBCs) make minor contributions to olfactory epithelium (OE) regeneration during homeostatic conditions, they possess a potent, latent capacity to activate and subsequently regenerate the OE following severe injury. Activation requires, and is mediated by, the downregulation of the transcription factor (TF) TP63. In this paper, we describe the cellular processes that drive the nascent stages of HBC activation. The compound phorbol 12-myristate 13-acetate (PMA) induces a rapid loss in TP63 protein and rapid enrichment of HOPX and the nuclear translocation of RELA, previously identified as components of HBC activation. Using bulk RNA sequencing (RNA-seq), we find that PMA-treated HBCs pass through various stages of activation identifiable by transcriptional regulatory signatures that mimic stages identified in vivo. These temporal stages are associated with varying degrees of engraftment and differentiation potential in transplantation assays. Together, these data show that our in vitro HBC activation system models physiologically relevant features of in vivo HBC activation and identifies new candidates for mechanistic testing.<br />Competing Interests: Declaration of interests J.E.S. is a co-founder of Rhino Therapeutics, Inc.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Transcription Factors metabolism
Transcription Factors genetics
Transcription Factor RelA metabolism
Olfactory Mucosa metabolism
Olfactory Mucosa cytology
Cell Differentiation genetics
Tetradecanoylphorbol Acetate pharmacology
Gene Expression Regulation
Gene Regulatory Networks
Subjects
Details
- Language :
- English
- ISSN :
- 2213-6711
- Volume :
- 19
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Stem cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 39059377
- Full Text :
- https://doi.org/10.1016/j.stemcr.2024.06.011