RNA-seq reveals transcriptome changes of the embryonic lens cells in Prox1 tissue specific knockout mice

Z.-Y. Yu, L. Wu, F.-K. Zhao, C. Peng, C.-X. Wang, B. Qu

Department of Ophthalmology, 4th Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Laboratory of Lens Research of Liaoning Province, Shenyang, China. dolphinemu@foxmail.com

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• Ophthalmology

OBJECTIVE: Prox1 is expressed in both lens epithelial cells and fiber cells and is essential for lens fiber cell elongation. This study aimed to explore the molecular mechanisms of how Prox1 mutations influence lens fiber cells development.
MATERIALS AND METHODS: Comparative transcriptomes analysis of Prox1 conditional knockout (cKO) lens and wild-type (WT) lens were performed using the data GSE69940 downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were determined by the R package “edgeR” of Trinity software. GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes databases) enrichment analysis were performed using the cluster Profiler R package. Then, the protein-protein interaction (PPI) network was predicted using Cytoscape, and the Module analysis of the PPI network was analyzed through the Cytoscape MCODE plugin. Moreover, MotifDb package in R was used to predict the transcription factors binding to Prox1 promoter regions.
RESULTS: In total, 2263 differentially expressed genes were identified between the two groups. GO and KEGG analysis showed that the down-regulated genes were enriched in camera-type eye term, nucleosome assembly, lens fiber cell differentiation, and cell modified and amino acid metabolism. The KEGG pathway of up-regulated genes was associated with lens development, including Hedgehog signaling pathway and MAPK signaling pathway. GO terms of up-regulated DEGs were mainly relevant to bone morphological development, muscle development, and sensory organ morphological development. Next, the PPI network of DEGs was constructed, and 4 modules were analyzed. Moreover, 30 transcription factors were predicted, which are likely to be downstream targets of Prox1 with potential roles in lens development in mice.
CONCLUSIONS: This study provides insights into the unique transcriptome profile of lens cells in Prox1 conditional knockout mice, which is a valuable resource for further study of mouse lens genomics.

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