PUBLICATION

Integrated scRNAseq analyses of mouse cochlear supporting cells reveal the involvement of Ezh2 in hair cell regeneration

Authors
Zhao, Y., Xu, Z., Zhang, R., Liu, M., Lu, C., Fan, C., Wang, J.
ID
ZDB-PUB-240129-1
Date
2024
Source
Molecular biology reports   51: 217217 (Journal)
Registered Authors
Fan, Chunxin
Keywords
EZH2, Hair cells regeneration, Single-cell transcriptome, Supporting cells, Transcriptional regulator
MeSH Terms
  • Animals
  • Cell Proliferation/genetics
  • Hair Cells, Auditory/metabolism
  • Mice
  • Signal Transduction/physiology
  • Single-Cell Gene Expression Analysis*
PubMed
38281217 Full text @ Mol. Biol. Rep.
Abstract
In lower vertebrates like fish, the inner ear and lateral line hair cells (HCs) can regenerate after being damaged by proliferation/differentiation of supporting cells (SCs). However, the HCs of mouse cochlear could only regenerate within one to two weeks after birth but not for adults.
To better understand the molecular foundations, we collected several public single-cell RNA sequencing (scRNAseq) data of mouse cochleae from E14 to P33 and extracted the prosensory and supporting cells specifically. Gene Set Enrichment Analysis (GSEA) results revealed a down-regulation of genes in Notch signaling pathway during postnatal stages (P7 and P33). We also identified 107 time-course co-expression genes correlated with developmental stage and predicated that EZH2 and KLF15 may be the key transcriptional regulators for these genes. Expressions of candidate target genes of EZH2 and KLF15 were also found in supporting cells of the auditory epithelia in chick and the neuromasts in zebrafish. Furthermore, inhibiting EZH2 suppressed regeneration of hair cells in zebrafish neuromasts and altered expressions of some developmental stage correlated genes.
Our results extended the understanding for molecular basis of hair cell regeneration ability and revealed the potential role of Ezh2 in it.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping