PUBLICATION
A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish
- Authors
- Jimenez, E., Slevin, C.C., Song, W., Chen, Z., Frederickson, S.C., Gildea, D., Wu, W., Elkahloun, A.G., Ovcharenko, I., Burgess, S.M.
- ID
- ZDB-PUB-221018-14
- Date
- 2022
- Source
- Cell genomics 2(9): (Journal)
- Registered Authors
- Burgess, Shawn, Jimenez, Erin
- Keywords
- none
- Datasets
- GEO:GSE192947
- MeSH Terms
- none
- PubMed
- 36212030 Full text @ Cell Genom
Citation
Jimenez, E., Slevin, C.C., Song, W., Chen, Z., Frederickson, S.C., Gildea, D., Wu, W., Elkahloun, A.G., Ovcharenko, I., Burgess, S.M. (2022) A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish. Cell genomics. 2(9):.
Abstract
Using adult zebrafish inner ears as a model for sensorineural regeneration, we ablated the mechanosensory receptors and characterized the single-cell epigenome and transcriptome at consecutive time points during hair cell regeneration. We utilized deep learning on the regeneration-induced open chromatin sequences and identified cell-specific transcription factor (TF) motif patterns. Enhancer activity correlated with gene expression and identified potential gene regulatory networks. A pattern of overlapping Sox- and Six-family TF gene expression and binding motifs was detected, suggesting a combinatorial program of TFs driving regeneration and cell identity. Pseudotime analysis of single-cell transcriptomic data suggested that support cells within the sensory epithelium changed cell identity to a "progenitor" cell population that could differentiate into hair cells. We identified a 2.6 kb DNA enhancer upstream of the sox2 promoter that, when deleted, showed a dominant phenotype that resulted in a hair-cell-regeneration-specific deficit in both the lateral line and adult inner ear.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping