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. 2024 Feb 21;627(8004):594–603. doi: 10.1038/s41586-024-07067-y

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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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Extended Data Fig. 7 — a, Volcano plot showing differential gene expression (log2 fold change ≥ 1) between patient Mutant and Corrected cells at day 16 (top) and day 32 (bottom). P-values for a two-group comparison were calculated using a two-sided Student’s t-test. b, Gene Set Enrichment Analysis (GSEA) plots showing the enrichment of up and downregulated genes in the set of genes annotated as GO “Cerebral Cortex Neuron Differentiation” at day 16 and (c) day 32. Mutant versus Mutant+Inhibitor IWP2 (1 mM (first pulse)/0.25 mM (second pulse)) are shown at the top and Corrected versus Corrected+Wnt3a (200 ng/ml) are shown at the bottom. Genes are ordered based on the differential expression values obtained from DESeq2. d, Gene Set Enrichment Analysis (GSEA) plots showing the enrichment of up and downregulated genes in the set of genes annotated as GO “Central Nervous System Neuron Differentiation” at day 16 and (e) day 32. Mutant versus Mutant+Inhibitor (IWP2) are shown at the top and Corrected versus Corrected+Wnt3a are shown at the bottom. Genes are ordered based on the differential expression values obtained from DESeq2. f, Heatmaps showing gene expression for critical neuronal genes in Mutant (Mut), Mutant+Inhibitor (IWP2) (Mut+I), Corrected (Corr) and Corrected+Wnt3a (Corr+W) at day 16 and (g) day 32. h, Heatmaps for differential gene expression (q = 0.01) of transcripts for signaling pathways, growth factors (GF) and genes that are members of the GO enrichment term “small GTPase mediated signal transduction” at day 32 of differentiation that are sensitive to Wnt signaling perturbations. Abbreviations: PDGF = PDGF growth factors; INS=insulin; NON.C.W= non canonical WNT. i, Heatmaps for differential gene expression (q = 0.01) (log2fold change, q = 0.01) of transcripts between the disease group (Mutant and Corrected+Wnt3a) and the Corrected group (Corrected and Mutant+Inhibitor (IWP2)) at day 16 and (j) day 32 of neuronal differentiation. k, Gene ontology (GO) analysis of genes differentially expressed (q ≤ 0.01) between the Corrected group (Corrected and Mutant+Inhibitor) and the disease group (Mutant and Corrected+Wnt3a) at day 16 (top) and (l) day 32 (bottom). Extracted from i and j.