Premature senescence and increased oxidative stress in the thymus of Down Syndrome patients

Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in down syndrome (DS) patients, normally seen in older healthy subjects. We then performed RNA-Seq analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased ?-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. Overall design: RNA-Seq analysis on sorted CD45- Epcam-enriched hTEC from DS patients and HD. Frozen samples of 3 normal HD and 3 DS patients were analyzed, for a total of 12 samples (Epcam+ and Epcam- for each of the 6 patients).