Dataset on transcriptome profiling of corneal endothelium from patients with Fuchs endothelial corneal dystrophy

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a bilateral inherited eye disease with advanced forms only treatable by corneal transplantation. The pathogenesis of FECD has not been worked out yet, however, trinucleotide repeat polymorphism CTG18.1 in the TCF4 gene has recently been associated with late-onset FECD. Gene expression profiling of corneal endothelium with and without this expansion can help elucidate molecular mechanisms of the disease development. Current data article represents whole transcriptome profiles of corneal endothelium obtained from 12 patients with FECD and 6 control tissues from eye bank donors. RNA sequencing data is available at NCBI Sequence Read Archive under Accession No. PRJNA524323. In addition, each patient and donor were genotyped for CTG18.1 expansion and the corresponding numbers of CTG repeats in the TCF4 gene are provided within this article. The dataset includes samples from FECD patients both with and without CTG18.1 expansion.

The Fuchs corneal dystrophy-associated CTG repeat expansion in the TCF4 gene affects transcription from its alternative promoters

“…To describe whether an increased CTG TNR affects the expression of different TCF4 transcripts, we performed a comprehensive analysis of two previously published RNA-seq datasets from the corneal endothelium of FECD patients with an expanded TCF4 CTG TNR and control groups without the repeat expansion 27 , 28 . The 2019 dataset generated by Nikitina et al includes 6 controls and 8 FECD patients with an expanded TCF4 CTG TNR 27 , and the 2020 dataset by Chu et al includes 9 controls and 6 FECD patients with an expanded TCF4 CTG TNR 28 . First, we evaluated how the levels of transcripts beginning from the CTG TNR region change in FECD.…”

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Figure 3 The expression of TCF4 alternative transcripts containing 5′ exons spliced to exon 4 is decreased in the cornea of FECD patients . Two independent FECD RNA-seq datasets—by Nikitina et al 27 (named 2019 in the figure) and Chu et al 28 (named 2020 in the figure)—were used to analyze the expression levels of TCF4 alternative 5′ exons in corneal endothelium. The expression levels of different TCF4 splicing events were quantified using the number of reads crossing the splice junction (shown above the graphs) normalized with the total number of spliced reads and multiplied by million.

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Figure 4 Expression of transcripts encoding TCF4-C isoform are downregulated, whereas transcripts encoding other TCF4 isoforms are upregulated in the cornea of FECD patients . Two independent FECD RNA-seq datasets—by Nikitina et al 27 (named 2019 in the figure) and Chu et al 28 (named 2020 in the figure)—were used to analyze the expression levels of TCF4 exons in corneal endothelium. The expression levels of ( A ) TCF4 isoforms and ( B ) internal exons were quantified using the number of reads ( A ) from transcripts encoding for the respective isoform (shown above the graphs) and ( B ) crossing the indicated splice junction (shown above the graphs).

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“…Detailed analysis of previously published FECD RNA-seq datasets 27 , 28 revealed that the levels of TCF4 transcripts containing alternative 5′ exons 4aI and 4aIII were reduced in the corneal endothelial cells of FECD patients with an expanded CTG TNR. These results support our findings that the TCF4 CTG TNR expansion reduces the activity of proximal downstream promoters linked to these 5′ exons also in human corneal endothelium.…”

“…No alterations in the overall expression of mature TCF4 mRNA was noted 28 . The study by Nikitina et al was a data article and no conclusions were made 27 .…”