Pluto Bioinformatics

GSE124197 (mouse): A Genome-wide CRISPR Screen Identifies Novel Genes Reinforcing Human Aging

Bulk RNA sequencing

A variety of cellular stresses including telomere erosion, genomic instability, DNA damage and heterochromatin alteration are increased during cell proliferation, and as a result cells enter senescence, which shows as a state of stable proliferative arrest. To identify genes controlling senescence, we present an unbiased CRISPR/Cas9 genetic screen for extending the life span of a premature aging disorder Werner Syndrome (WS) human mesenchymal stem cells (hMSCs). Here, we identify several genes including lysine acetyltransferase 7 (KAT7) that reinforce aging. While knockdown KAT7 alleviates premature aging of WS hMSCs. Notably, except the WS hMSCs, knockdown KAT7 also extends the life-span of Hutchinson-Gilford Progeria Syndrome (HGPS) hMSCs and replicative senescent (RS) hMSCs. Conversely, ectopic expression of KAT7 in hMSCs results in premature senescence partially via acetylated the lysine residue of H3K14 and then upregulated genes expression which increased during aging as well as the enrichment of H3K14ac was also increased. Even chromatin shows lots of inactivated consistent with lower gene expression after knockdown KAT7. Moreover, we show that a genomic CRISPR/Cas9 screen can precisely identify functional genes which reinforcing aging and uncover a role of KAT7 in maintaining euchromatin stability and highlight euchromatin disorganization as a potential determinant of human aging. SOURCE: GEO admin (geo@ncbi.nlm.nih.gov) - NCBI/NLM/NIH