Elucidating the genetic drivers of accelerated cellular ageing in Down syndrome

How DNA variants, including aneuploidy and copy number variations, impact brain and organ development, or cause disease later in life, is largely unclear. Here we propose to quantify and deconstruct senescence of iPSC-derived Down syndrome mesenchymal stem cells at a single cell level. By performing an unbiased combinatorial CRISPR-KO and CRISPR repression screens we aim to discover the HSA 21 genes collectively responsible for accelerated senescence of trisomy 21 mesenchymal stem cells.