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Fig. 9 | Acta Neuropathologica Communications

Fig. 9

From: In Parkinson's patient-derived dopamine neurons, the triplication of α-synuclein locus induces distinctive firing pattern by impeding D2 receptor autoinhibition

Fig. 9Fig. 9Fig. 9

The transcriptome network and immunostaining for D2R and GIRK channels. a D2R pathway showed overall upregulation in AST-derived dopamine neurons with most elements in the D2R signaling cascade, such as Gβγ, increased in relative expression (red). Green indicates downregulation and gray indicates no change. Key to abbreviations provided in Additional file 3: Table S1. b A transcriptome network for GIRK in AST-derived neurons. Overall, there was an increase in this network. Red indicates that the transcript is increased in abundance and blue indicates that transcript is decreased in relative abundance compared to NAS. Gray indicates an entity or gene that was not measured or detected in derived neurons. Abbreviations are provided in B. c Analysis of bulk RNA sequencing of AST-derived dopamine neurons (n = 3) and NAS-derived dopamine neurons (n = 3) revealed 1512 differetially expressed genes with 916 decreased in AST-dervied dopamine neurons (log2(Fold change) < -1, p < 0.05) and 596 increased in AST-derived dopamine neurons (log2(Fold change > 1, p < 0.05). d Gene set enrichment analysis (GSEA) depicted as a volcano plot revealed genes associated with dopamine/Gs signaling were upregulated in AST-derived vs NAS-derived dopamine neurons (Median fold change > 1.5, p < 0.05). e Immunostaining for GIRK2 channel (Kir3.2) and D2R after 5 months differentiation of NAS and AST. f top. Parallel immunostaining via a blinded experimental design, revealed a lower Kir3.2 expression in AST-derived neurons than in NAS-derived neurons (t257 = 14.01, p < 0.001, two-tailed Student's t tests, n: NAS = 126, AST = 133). Bottom. Parallel immunostaining showed a reduced D2R expression in the AST-derived neurons compared with NAS-derived neurons (t259 = 13.59, p < 0.001, two-tailed Student's t tests, n: NAS = 136, AST = 125)

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