Transcriptomic analysis of differential gene expression during chick periocular neural crest differentiation into corneal cells
Transcriptomic analysis of differential gene expression during chick periocular neural crest differentiation into corneal cells
复制标题
DOI：
10.1002/dvdy.43
复制
发表时间：
2019-07-01
影响因子：
2.5
通讯作者：
Lwigale, Peter
中科院分区：
文献类型：
--
作者：
Bi, Lian;Lwigale, Peter
多能神经嵴细胞（NCC）在眼发育过程中对角膜内皮细胞和角膜基质细胞有重要作用，但其分子机制尚不清楚。我们对眼周神经嵴（pNC）、角膜内皮和角膜细胞进行了RNA-Seq分析，并通过原位杂交验证了候选基因的表达。结果RNA-Seq分析显示pNC和神经嵴来源的角膜细胞之间的基因富集，其对应于参与粘着斑、ECM-受体相互作用、细胞粘附、黑素生成和MAPK信号传导的途径。候选NCC基因与眼基因表达的比较显示，大多数NCC基因在pNC中表达，但它们在角膜发育期间差异表达或维持。参与视黄酸、转化生长因子-β和Wnt信号通路及其调节剂的几个基因也差异表达。我们确定了差异表达的转录因子作为潜在的下游候选者，可能指导参与建立角膜内皮细胞和角膜基质细胞身份的基因表达。结论pNC向高度分化的角膜内皮细胞和角膜基质细胞分化过程中基因表达谱发生了新的变化。这些数据可作为进一步分析NCC分化为角膜细胞所涉及的分子网络的平台，并为角膜发育不全和成人疾病所涉及的基因提供见解。
Background Multipotent neural crest cells (NCC) contribute to the corneal endothelium and keratocytes during ocular development, but the molecular mechanisms that underlie this process remain poorly understood. We performed RNA-Seq analysis on periocular neural crest (pNC), corneal endothelium, and keratocytes and validated expression of candidate genes by in situ hybridization. Results RNA-Seq profiling revealed enrichment of genes between pNC and neural crest-derived corneal cells, which correspond to pathways involved in focal adhesion, ECM-receptor interaction, cell adhesion, melanogenesis, and MAPK signaling. Comparisons of candidate NCC genes to ocular gene expression revealed that majority of the NCC genes are expressed in the pNC, but they are either differentially expressed or maintained during corneal development. Several genes involved in retinoic acid, transforming growth factor-beta, and Wnt signaling pathways and their modulators are also differentially expressed. We identified differentially expressed transcription factors as potential downstream candidates that may instruct expression of genes involved in establishing corneal endothelium and keratocyte identities. Conclusion Combined, our data reveal novel changes in gene expression profiles as pNC differentiate into highly specialized corneal endothelial cells and keratocytes. These data serve as platform for further analyses of the molecular networks involved in NCC differentiation into corneal cells and provide insights into genes involved in corneal dysgenesis and adult diseases.