The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS.

FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis / DE SANTIS, Riccardo; Santini, Laura; Colantoni, Alessio; Peruzzi, Giovanna; DE TURRIS, Valeria; Alfano, Vincenzo; Bozzoni, Irene; Rosa, Alessandro. - In: STEM CELL REPORTS. - ISSN 2213-6711. - (2017), pp. ...-.... [10.1016/j.stemcr.2017.09.004]

FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis

DE SANTIS, RICCARDO;SANTINI, LAURA;COLANTONI, ALESSIO;PERUZZI, Giovanna;DE TURRIS, VALERIA;ALFANO, VINCENZO;BOZZONI, Irene;ROSA, ALESSANDRO
2017

Abstract

The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases. Several microRNAs (miRNAs) were also deregulated in FUS mutant motoneurons, including miR-375, involved in motoneuron survival. We report that relevant targets of miR-375, including the neural RNA-binding protein ELAVL4 and apoptotic factors, are aberrantly increased in FUS mutant motoneurons. Characterization of transcriptome changes in the cell type primarily affected by the disease contributes to the definition of the pathogenic mechanisms of FUS-linked ALS.
2017
ALS; ELAVL4; FUS/TLS; amyotrophic lateral sclerosis; iPSC; induced pluripotent stem cells; miR-375; microRNA; motoneuron; p53
01 Pubblicazione su rivista::01a Articolo in rivista
FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis / DE SANTIS, Riccardo; Santini, Laura; Colantoni, Alessio; Peruzzi, Giovanna; DE TURRIS, Valeria; Alfano, Vincenzo; Bozzoni, Irene; Rosa, Alessandro. - In: STEM CELL REPORTS. - ISSN 2213-6711. - (2017), pp. ...-.... [10.1016/j.stemcr.2017.09.004]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1010900
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