A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish.

Autor:	Jimenez E; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA., Slevin CC; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA., Song W; Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA., Chen Z; CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.; Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, China., Frederickson SC; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA., Gildea D; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA., Wu W; Vaccine Immunology Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Elkahloun AG; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA., Ovcharenko I; Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA., Burgess SM; Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, MD, USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2022 Sep 14; Vol. 2 (9). Date of Electronic Publication: 2022 Aug 22.
DOI:	10.1016/j.xgen.2022.100170
Abstrakt:	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. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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