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• W3000943614 endingPage "129540" @default.
• W3000943614 startingPage "129540" @default.
• W3000943614 abstract "Current experimental models using either human or mouse cell lines, are not representative of the complex features of GBM. In particular, there is no model to study patient-derived iPSCs to generate a GBM model. Overexpression of c-met gene is one of the molecular features of GBM leading to increased signaling via STAT3 phosphorylation. We generated an iPSC line from a patient with c-met mutation and we asked whether we could use it to generate neuronal-like organoids mimicking features of GBM.We have generated iPSC-aggregates differentiating towards organoids. We analyzed them by gene expression profiling, immunostaining and transmission electronic microscopy analyses (TEM).Herein we describe that c-met-mutated iPSC aggregates spontaneously differentiate into dopaminergic neurons more rapidly than control iPSC aggregates in culture. Gene expression profiling of c-met-mutated iPSC aggregates at day +90 showed neuronal- and GBM-related genes, reproducing a genomic network described in primary human GBM. Comparative TEM analyses confirmed the enrichment of these structures in intermediate filaments and abnormal cilia, a feature described in human GBM. The c-met-mutated iPSC-derived organoids, as compared to controls expressed high levels of glial fibrillary acidic protein (GFAP), which is a typical marker of human GBM, as well as high levels of phospho-MET and phospho-STAT3. The use of temozolomide (TMZ) showed a preferential cytotoxicity of this drug in c-met-mutated neuronal-like organoids.This study shows the feasibility of generating off-the shelf neuronal-like organoid model mimicking GBM using c-met-mutated iPSC aggregates and its potential future use in research." @default.
• W3000943614 created "2020-01-30" @default.
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• W3000943614 date "2020-04-01" @default.
• W3000943614 modified "2023-10-10" @default.
• W3000943614 title "A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC)" @default.
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• W3000943614 doi "https://doi.org/10.1016/j.bbagen.2020.129540" @default.
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