Abstract：
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: Our results extended the understanding for molecular basis of hair cell regeneration ability and revealed the potential role of Ezh2 in it.
RESULTS: 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.
CONCLUSIONS: Our results extended the understanding for molecular basis of hair cell regeneration ability and revealed the potential role of Ezh2 in it.
摘要：
背景：在鱼类等低等脊椎动物中，内耳和侧线毛细胞（HCs）在被支持细胞（SCs）的增殖/分化损害后可以再生。然而,小鼠耳蜗的HC只能在出生后一到两周内再生，但成年人则不能再生。
结果：为了更好地理解分子基础，我们从E14到P33收集了一些小鼠耳蜗的公开单细胞RNA测序（scRNAseq）数据，并专门提取了前感和支持细胞。基因集富集分析(GSEA)结果显示在出生后阶段Notch信号通路中的基因下调(P7和P33)。我们还鉴定了107个与发育阶段相关的时程共表达基因，并预测EZH2和KLF15可能是这些基因的关键转录调节因子。EZH2和KLF15的候选靶基因的表达也在小鸡的听觉上皮的支持细胞和斑马鱼的神经桅杆中被发现。此外，抑制EZH2抑制斑马鱼神经菌根毛细胞再生，并改变一些发育阶段相关基因的表达。
结论：我们的结果扩展了对毛细胞再生能力的分子基础的理解，并揭示了Ezh2在其中的潜在作用。
结果：为了更好地理解分子基础，我们从E14到P33收集了一些小鼠耳蜗的公开单细胞RNA测序（scRNAseq）数据，并专门提取了前感和支持细胞。基因集富集分析(GSEA)结果显示在出生后阶段Notch信号通路中的基因下调(P7和P33)。我们还鉴定了107个与发育阶段相关的时程共表达基因，并预测EZH2和KLF15可能是这些基因的关键转录调节因子。EZH2和KLF15的候选靶基因的表达也在小鸡的听觉上皮的支持细胞和斑马鱼的神经桅杆中被发现。此外，抑制EZH2抑制斑马鱼神经菌根毛细胞再生，并改变一些发育阶段相关基因的表达。
结论：我们的结果扩展了对毛细胞再生能力的分子基础的理解，并揭示了Ezh2在其中的潜在作用。
