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. 2024 Apr 22;14:9177. doi: 10.1038/s41598-024-59834-6

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© The Author(s) 2024

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Observation of ER stress and UPR activation in iPSCs-derived neuronal cells from GD. (a) (Top) Bar graphs representing the relative mRNA expression levels of BiP (left, Kruskal–Wallis test: H(2) = 8.20, p = 0.02 for Control vs. GD3-1, p = 0.03 for Control vs. GD3-2, n = 6 technical replicates), CHOP (middle, Kruskal–Wallis test: H(2) = 8.24, p < 0.01 for Control vs. GD3-1, p = 0.02 for Control vs. GD3-2, n = 6 technical replicates) and ATF4 (right, Kruskal–Wallis test: H(2) = 8.20, p = 0.02 for Control vs. GD3-1, p = 0.01 for Control vs. GD3-2, n = 6 technical replicates) in NPCs from control, GD3-1 and GD3-2 samples. (Bottom) Bar graphs representing the relative mRNA expression levels of BiP (left, Kruskal–Wallis test: H(2) = 15.73, p = 0.04 for Control vs. GD3-1, p = 0.04 for Control vs. GD3-2, n = 6 technical replicates), CHOP (middle, Kruskal–Wallis test: H(2) = 7.55, p = 0.11 for Control vs. GD3-1, p < 0.01 for Control vs. GD3-2, n = 5 technical replicates) and ATF4 (right, Kruskal–Wallis test: H(2) = 12.75, p = 0.02 for Control vs. GD3-1, p = 0.21 for Control vs. GD3-2, n = 6 technical replicates) in iPSCs-derived neuronal cells from control, GD3-1 and GD3-2 samples. (b) (Top) Representative cropped western blot images of GBA1 and CHOP from iPSCs-derived neuronal cells from control, GD3-1 and GD3-2 samples. (Bottom) Bar graphs summarizing of the relative normalized BiP (Kruskal–Wallis test: H(2) = 11.9, p < 0.01 for Control vs. GD3-1, p < 0.01 for Control vs. GD3-2, n = 6 technical replicates) and CHOP (Kruskal–Wallis test: H(2) = 6.24, p = 0.04 for Control vs. GD3-1, p = 0.03 for Control vs. GD3-2, n = 5 technical replicates) protein expression in GD3-1 and GD3-2 compared to control group. (c) Representative cropped western blot images of Bax (left) and Bcl-2 (right) from iPSCs-derived neuronal cells from control, GD3-1 and GD3-2 samples. (d) Bar graphs summarizing of the relative normalized Bax (Kruskal–Wallis test: H(2) = 7.09, p = 0.02 for Control vs. GD3-1, p = 0.03 for Control vs. GD3-2, n = 7 technical replicates) , Bcl-2 (Kruskal–Wallis test: H(2) = 5.46, p = 0.06, n = 7 technical replicates) and the ratio of Bax/Bcl-2 (Kruskal–Wallis test: H(2) = 7.93, p < 0.01 for Control vs. GD3-1, p = 0.36 for Control vs. GD3-2, n = 7 technical replicates) protein expression in GD3-1 and GD3-2 compared to control group. All replicate western blot images are included in the supplementary information file.