Efficient Induction of U87 Differentiation into Neurons by Small Molecules.
The investigation of effective, prompt, and universally applicable strategies for inducing the differentiation of glioblastoma (GBM) into terminally differentiated cells, such as astrocytes or neurons that cease cell division, has become a crucial aspect of GBM differentiation therapy, aiming to reduce the risk of recurrence.The utilization of a small-molecule cocktail, known as YFSS (Y27632, Forskolin, SB431542, and SP600125), which selectively targets the ROCK, cAMP, TGF-ß, and JNK signaling pathways, respectively, successfully induced differentiation in human GBM cell line U87 within 7 days.Transcriptome sequencing analysis provided insights into the signaling pathways implicated in YFSS-induced differentiation, encompassing both cellular proliferation and neuronal differentiation. This study, which delved into approaches to rapidly and efficiently induce neuronal differentiation of GBM cells, and provided a thorough understanding of the underlying molecular mechanisms, holds great promise as a novel and encouraging strategy for the treatment of GBM. Overall design: In order to gain a deeper understanding of the molecular mechanism underlying the differentiation of GBM cells into neurons induced by YFSS, an intergroup correlation analysis (WGCNA, GO, KEGG and GSEA) was conducted on the differentially expressed gene sets within the U87 transcriptome at multiple time points (0, 1, 3, 5, and 7 days).