Abstract
Purpose :
The lens transcriptome has been examined by microarrays and RNA-sequencing (RNA-seq). These omics data are the basis of the bioinformatics web-resource iSyTE, which has identified new cataract-linked genes. However, the lens comprises of epithelial and fiber cells, yet presently, iSyTE is based on whole lens data. To enable cell type-specific resolution, we meta-analyzed isolated lens epithelium and fiber transcriptome datasets for integration in iSyTE.
Methods :
Isolated mouse lens epithelium and fiber transcriptome public datasets at embryonic (E) and postnatal (P) stages E12.5, E14.5, E16.5, E18.5, P0.5, P0, P5, P13, and age 1 month, 3 months, 6 months, and 2 years were analyzed. Microarray or RNA-seq data were analyzed by appropriate methods and compared to other resources (e.g., Cat-Map).
Results :
Across all the stages, ~2000 genes are differentially expressed between epithelium and fibers, of which ~4% are linked to cataract in Cat-Map. Gene ontology enrichment validates epithelial- and fiber-expected expression, corroborating the meta-analysis. Whole embryonic-body (WB)-in silico subtraction identifies high-priority epithelial- and fiber-enriched genes. Further, new insights at specific stages were obtained (e.g., ribonucleoprotein regulatory processes are enriched in E12.5 epithelium), predicting distinct regulatory relationships in epithelium and fibers. Finally, this meta-analyzed data is rendered user-friendly and freely accessible at iSyTE (https://research.bioinformatics.udel.edu/iSyTE/).
Conclusions :
This meta-analysis advances our knowledge on the spatiotemporal transcriptome changes in isolated lens epithelium and fibers. Additionally, this is the first report providing detailed analysis of epithelium and fibers in early lens development (E12.5). These new lens cell-type specific knowledge will facilitate iSyTE-based cataract gene discovery.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.