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. 2022 Aug 18;8:106. doi: 10.1038/s41531-022-00369-w

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a, b q-rt-PCR data from midbrain of mice lacking Esrrg (AAV-hsynCre Esrrg^fl/fl vs. AAV-hsynCre Esrrg^+/+) or of mice overexpressing Esrrg (AAV-Esrrg vs. AAV-Gfp) (n = 7–8/group; two-tailed unpaired t-test *p < 0.05, **p < 0.01). c Representative images from sm-FISH for Th (red), Esrrg (white), endogenous GFP-L10a (green), and DAPI (blue) in Esrrg^+/+;L10+ and Esrrg^fl/fl; L10+ mice injected with AAV:ThCre to induce the Gfp-Rpl10a transgene in DAergic neurons. d q-rt-PCR from BAC-TRAP pulldowns for Th, Gad65 and Esrrg transcript for confirmation of enrichment of DAergic markers and exclusion of inhibitory neuron markers (n = 2–3/group; one-way ANOVA with Tukey’s post hoc analysis **p < 0.01, ***p < 0.001). e Volcano plot showing differentially expressed genes in AAV:ThCre-injected Esrrg^+/+;L10+ and Esrrg^fl/fl; L10+ mice after sequencing (gray = no significance, green = ±1.5 log₂-fold change, blue = significant p^adj value, red = significant p^adj value and differentially expressed ±1.5 log₂-fold change). f Fold control expression of genes downregulated with Esrrg deletion by functional category. g Fold control of ETC genes reduced in PD patients that had significant p^adj values but not ±1.5 log₂ fold change. h Pie chart demonstrating overlap between genes changed with Esrrg overexpression in SH-SY5Ys and genes changed with Esrrg knockout with BAC-TRAP. Q-rt-PCR with Esrrg knockout or overexpression from genes identified as putative targets of Esrrg (n = 5–8 mice/group; two-tailed unpaired t-tests *p < 0.05, **p < 0.01). i Overlap of predicted PD GWAS and QTL genes and genes changed with Esrrg knockout using BAC-TRAP in DAergic neurons. qPCR from targets in both Esrrg knockout and overexpression in the midbrain (n = 5–8 mice; two-tailed unpaired t-test *p < 0.05). j, k sm-FISH for the identified targets Kcns3 and Dgkq at both 1 and 6 months P.I. of AAV-ThCre (n = 3–4/group; two-tailed unpaired t-test *p < 0.05, **p < 0.01). l q-rt-PCR from Esrrg knockout (AAV-hsynCre) or overexpression (AAV-Esrrg) midbrain homogenate for autophagy and microtubule and vesicle-related genes (n = 5–8 mice/group; two-tailed unpaired t-test *p < 0.05, **p < 0.01, ***p < 0.001). Numbers on bars are cell counts from each experimental group. Scale bars correspond to 50 µm (c). Error bars represent ± SEM.