Research Paper Volume 11, Issue 12 pp 4011—4031

A large-scale CRISPR screen and identification of essential genes in cellular senescence bypass

Figure 4. Transcriptomes of senescence bypass cells exhibited different patterns. (A) Fold changes of gene expressions of the senescence bypass cells compared with senescent cells. All differential expression genes (adjusted p-value < 0.05) between senescent samples and samples knocking-out validated genes were shown. Genes were clustered by k-means methods with k = 7. (BC) KEGG pathway and GO enrichment results of genes in Cluster 1 and Cluster 5 respectively. Terms with adjusted p-value < 10–5 were shown. (D) Fold changes of SASP gene expression compared with senescent cells. Genes with significantly up-regulated in senescent cells compared with normal growing cells were shown (adjust p-value < 0.05). (E) Normalized expression profiles of IL1A, IL8, and MMP1 across all RNA-seq samples. Grey lines indicated the average expression in senescent samples. (F) GSEA analysis of growing, MTOR-deficiency, CRISPLD2-deficiency, and MORF4L1-deficiency samples in the geneset up-regulated by NF-κB (HINATA_NFKB_TARGETS_FIBROBLAST_UP), KEGG pathways of Alzheimer’s disease (KEGG_AD), Huntington’s disease (KEGG_HD), and Parkinson’s disease (KEGG_PD). GSEA was performed using ranked DESeq2 Wald statistics compared with senescent cells.