Figure 7.

Human Cockayne syndrome and trichothiodystrophy (TTD)-derived cells mimic age-associated decrease in the expression of long genes

(A) Experimental approach: skin fibroblasts were extracted from a Cockayne syndrome (ERCC6^mut) patient and reprogrammed to generate induced pluripotent stem cells (iPSCs), gene-corrected using CRISPR-Cas9 (ERCC6^GC), and differentiated to mesenchymal stromal cells (MSCs). The transcriptome of ERCC6^mut and ERCC6^GC MSCs was analyzed using RNAseq in basal conditions and after UV-radiation exposure.

(B and C) Baseline effect of the Cockayne syndrome group B (ERCC6) mutation on length-dependent expression. (B) Boxplots showing the length of the top 300 DEGs between mutant (ERCC6^mut) and gene-corrected (ERCC6^GC) cells in normal conditions (control) and after UV-radiation exposure. Whiskers extend to the furthest datapoint within the 1.5∗IR. (C) Average gene expression of mutant against gene-corrected cells in basal conditions and after UV-radiation exposure.

(D and E) Effect of UV-radiation on cells carrying the ERCC6 mutation and gene-corrected cells. (D) Boxplots showing the length of the top 300 DEGs between cells with and without UV-radiation exposure. Whiskers extend to the furthest datapoint within the 1.5∗IR. (E) Average gene expression in UV-radiated cells against cells in basal conditions.

(F) Experimental approach: dermal fibroblasts from a PS-TTD patient (ERCC2^mut) and her healthy mother were extracted and analyzed using RNAseq.

(G and H) Length of the DEGs (|logFC| ≥ 2 and p value ≤ 0.05) between PS-TTD cells and healthy cells in basal conditions (G) and upon UV-radiation (H). Whiskers extend to the furthest datapoint within the 1.5∗IR.

See also Table S5.