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• W3048669809 abstract "Summary Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is often caused by an adenine to guanine mutation at m.3243 (m.3243A>G) of the MT-TL1 gene (tRNA leu(UUR) ). To understand how this mutation affects the nervous system, we differentiated human induced-pluripotent stem cells (iPSCs) into excitatory neurons with normal (low heteroplasmy) and impaired (high heteroplasmy) mitochondrial function from MELAS patients with the m.3243A>G mutation. We combined micro-electrode array (MEA) measurements with RNA sequencing (MEA-seq) and found that the m.3243A>G mutation affects expression of genes involved in mitochondrial respiration- and presynaptic function, as well as non-cell autonomous processes in co-cultured astrocytes. Finally, we show that the clinical II stage drug sonlicromanol (KH176) improved neuronal network activity in a patient-specific manner when treatment is initiated early in development. This was intricately linked with changes in the neural transcriptome. Overall, MEA-seq is a powerful approach to identify mechanisms underlying the m.3243A>G mutation and to study the effect of pharmacological interventions in iPSC-derived neurons. Highlights - High m.3243A>G heteroplasmy leads to lower neuronal network activity and synchronicity - High heteroplasmy affects expression of genes involved in mitochondrial ATP production and the synaptic function / the presynaptic vesicle cycle - High neuronal heteroplasmy non cell autonomously affects gene expression in healthy co-cultured astrocytes - Sonlicromanol partially rescues neuronal network activity and transcriptome changes induced by high heteroplasmy eTOC Blurb Using human inducible pluripotent stem cell-derived neurons with high levels of m.3243A>G heteroplasmy, Klein Gunnewiek et al. show transcriptome changes underlying the functional neuronal network phenotype, and how sonlicromanol can partially improve both this neuronal network phenotype, and the transcriptome changes, in a patient-specific manner." @default.
• W3048669809 created "2020-08-18" @default.
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• W3048669809 date "2020-08-12" @default.
• W3048669809 modified "2023-10-17" @default.
• W3048669809 title "Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A>G heteroplasmy in iPSC-derived neurons" @default.
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• W3048669809 cites W1645300466 @default.
• W3048669809 cites W1874684536 @default.
• W3048669809 cites W1966418641 @default.
• W3048669809 cites W1967646152 @default.
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• W3048669809 cites W2003931544 @default.
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• W3048669809 cites W2012935976 @default.
• W3048669809 cites W2017592329 @default.
• W3048669809 cites W2020985206 @default.
• W3048669809 cites W2024530489 @default.
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• W3048669809 cites W2131271579 @default.
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• W3048669809 cites W2134807790 @default.
• W3048669809 cites W2135335338 @default.
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• W3048669809 doi "https://doi.org/10.1101/2020.08.11.246140" @default.
• W3048669809 hasPublicationYear "2020" @default.
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