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
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
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hg138
    		Indel
    hg139
      		Indel
      hg140
        		Indel
        hg148TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          sox2CRISPR11-sox2CRISPR
          sox2CRISPR12-sox2CRISPR
          sox2CRISPR13-sox2CRISPR
          sox2CRISPR8-sox2CRISPR
          sox2CRISPR9-sox2CRISPR
          sox2CRISPR10-sox2CRISPR
          1 - 6 of 6
          Show
          Fish
          No data available
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab11-sox2polyclonal
            		IgGRabbit
            1 - 1 of 1
            Show
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            1 - 1 of 1
            Show
            Mapping
            No data available
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            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):.