Chemical screen identifies a geroprotective role of quercetin in premature aging

Geng, Lingling; Liu, Zunpeng; Zhang, Weiqi; Li, Wei; Wu, Zeming; Wang, Wei; Ren, Ruotong; Su, Yao; Wang, Peichang; Sun, Liang; Ju, Zhenyu; Chan, Piu; Song, Moshi; Qu, Jing; Liu, Guang-Hui

To uncover the molecular mechanisms by which Que rejuvenated WS hMSCs, we performed genome-wide RNA sequencing (RNA-seq). The correlation coefficients between replicates were 0.9999 in vehicle-(Ctrl) and Que-treated WS hMSCs, indicating that the RNA-seq data were of high reproducibility (Fig. 6A) . A total of 486 upregulated genes and 294 downregulated genes were obtained in Que-treated WS hMSCs relative to Ctrl (|Log 1.5 (fold change)| > 1, adjust P value (padj) < 0.05) (Fig. 6B , 6C, Tables S2 and S3). Protein-protein interactions (PPI) network of differentially expressed genes was drawn based on the STRING database (Fig. 6D ). Gene Ontology (GO) analysis revealed that the upregulated genes in Que-treated WS hMSCs were enriched in biological processes including cell cycle, cell division, chromosome segregation, and cell proliferation ( Fig. 6E and 6F). Consistently, gene set enrichment analysis (GSEA) data revealed that Que-treated WS hMSCs were enriched in GO terms including cell cycle, condensed chromosome, as well as cellular response to oxygen, UV and vitamin ( Fig. 6F and 6G ). On the contrary, vehicle-treated WS hMSCs were enriched in apoptosis pathway (Fig. 6G ). The anti-apoptotic function of Que was further evidenced by the increased transcriptional levels of typical anti-apoptotic genes including genes in BCL2, IAP and AKT families (Fig. 6F) , consistent with the aforementioned results showing decreased cell apoptosis in Que-treated WS hMSCs.