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Efficient Induction of U87 Differentiation into Neurons by Small Molecules.

ABSTRACT: Efficient Induction of U87 Differentiation into Neurons by Small Molecules.

PROVIDER: PRJNA1040879 | ENA |

REPOSITORIES: ENA

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Efficient Induction of U87 Differentiation into Neurons by Small Molecules.

Project description: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-β, 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.

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Direct Induction of Neurons from Various Cell Types by Chemical Defined Medium

Project description:We have developed a serum-free chemical defined medium, namely 6C, that can directly convert mouse embryonic fibroblast (MEFs), glia cells into neurons in vitro. Human cells such as human foreskin fibroblast(HHFs), Hela cells and born marrow derived mesenchymal stem cells (BM-hMSC) can also be converted into neuron-like cells by this medium with some modification such as including several other small molecules. To understand the possible mechanisms, the transdifferentiation of MEFs by 6C was chosen as a model system and gene profiling at different time point during the conversion was carried out by RNA sequencing using Illumina MiSeq. MEFs was maintained in MEF medium (DMEM containing 10% FBS, 1mM Glutamax and 100X NEAA), to start the induction, the culture medium was shift to 6C and marked as day 0, neurons could be generated in day 15. mRNA samples was collected at day 0, 2, 5, 10, 15 during the process, with cell lysed by Trizol and mRNA enriched by Illumina TruSeq RNA Sample Preparation v2 kit. We find that most cell cycle related genes were up regulated during the first few days of induction, while many Notch pathway genes up regulated during the later phase of this process. The RNA sequencing data provided important cues for further study on the mechanisms of the direct neuronal induction process. Gene profiling at different time point during the transdifferentiation mediated by 6C medium.

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