Differential gene expression in immortalised fibroblasts derived two independent Nestor Guillermo Progeria Syndrome (NGPS) patients, compared to immortalised fibroblasts of an healthy individual

Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Through a whole genome, multiparametric CRISPR anti-aging screen,we identified 43 new genes that can reverse multiple aging phenotypes in progeria. The screen was implemented in fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) patients, carrying a homozygous p.Ala12Thr mutation in barrier-to-autointegration factor (BAF A12T). The hits were enriched for genes involved in protein synthesis, protein and RNA transport and osteoclast formation. We further confirmed that BAF A12T drives increased protein translation and translational errors that could directly contribute to premature aging in patients. This RNA seq analysis identified 213 genes as being differentially expressed in NGPS cells compared to WT cells. GO analysis showed enrichment for genes involved in translation, supporting that the BAF A12T mutation modulates the expression of genes regulating translation Overall design: We extracted RNA from NGPS 1 and 2 fibroblasts, as well as from wild type cells. We then compared genes that were differentially expressed in NGPS cells compared to WT