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. 2021 Oct 8;12:5907. doi: 10.1038/s41467-021-26066-5

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© The Author(s) 2021

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. 2 — a The volcano plot resulted by the differentially gene expression (DGE) analysis between Substantia Nigra Brain-Chip and conventional cell cultures. For the selection of the DE genes we used the following thresholds: adjusted (adj) p-value < 0.05 and |Log2(foldchange)| >1. The identified up- (down-) regulated genes are highlighted in cyan (magenta) color respectively. Sample sizes were as follows: Substantia Nigra Brain-Chip, n = 4, conventional cell culture system, n=4. The p-values attained by the two-sided Wald test and corrected for multiple testing using the Benjamini and Hochberg method. b, c List of biological processes identified by Gene Ontology (GO) enrichment analysis using the up- and downregulated genes respectively resulted by the differentially gene expression analysis between Substantia Nigra Brain-Chip and conventional cell cultures. d DGE analysis identified up- and downregulated genes in Substantia Nigra Brain-Chip compared to conventional cell cultures (cyan circle), and human adult substantia nigra compared to conventional cell cultures (yellow circle). Sample sizes were as follows: Substantia Nigra Brain-Chip, n = 4, Conventional cell culture system, n = 4, and adult substantia nigra, n = 8 (independent biological specimens). Culture in Brain-Chips and conventional cell cultures were done in parallel. Samples were collected and processed for analyses 8 days post-seeding (D8). e Gene expression pattern analysis between the following groups: i) Adult Substantia Nigra vs. Brain-Chip and ii) Adult Substantia Nigra vs. Conventional Cell Culture system. In the Brain-Chip, most of these genes (those with an asterisk) exhibit statistically significantly smaller fold changes (P < 0.05) in their expression levels as compared to the conventional cell culture system. Statistical analysis is two-sided Wald test and corrected for multiple testing using the Benjamini and Hochberg method. The adjusted P value per gene is contained in Supplementary Table 1.