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Subcellular localization of KAT5 in human iPSC-derived WT and FAD neurons. Induced-pluripotent stem cells (iPSCs) from a WT CViia2 strain, APP Swedish (APPswed) and APP duplication mutants (APPdup, a model of trisomy 21) were differentiated into glutamatergic neurons and stained for KAT5 (green), <t>DAPI</t> (blue) to show nuclear localization and MAP2 (red) to show cytosolic cytoskeletal structure. The wild-type cells demonstrate ubiquitous localization (A) with fluorescent overlap with the DAPI nuclear signal. All explored FAD mutant lines (B and C) and APP duplication lines (D) show specific nuclear exclusion of KAT5. The WT CViia2 neurons treated with gamma-secretase inhibitor DAPT demonstrate nuclear exclusion of KAT5 (E). The statistical significance was analyzed as described in methods section across cells per culture group, with the average for each cell-type shown as a single dot in the plots on the right (F and G). The WT cells are statistically significantly different in nuclear signal intensity than either the APPSWE heterozygous cells (p<0.01), the APP duplication (p<0.05), and PSEN2 N141I heterozygous mutants (p<0.01). The gamma-secretase inhibitor treated cells approached statistical significance (p<0.09).
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Subcellular localization of KAT5 in human iPSC-derived WT and FAD neurons. Induced-pluripotent stem cells (iPSCs) from a WT CViia2 strain, APP Swedish (APPswed) and APP duplication mutants (APPdup, a model of trisomy 21) were differentiated into glutamatergic neurons and stained for KAT5 (green), DAPI (blue) to show nuclear localization and MAP2 (red) to show cytosolic cytoskeletal structure. The wild-type cells demonstrate ubiquitous localization (A) with fluorescent overlap with the DAPI nuclear signal. All explored FAD mutant lines (B and C) and APP duplication lines (D) show specific nuclear exclusion of KAT5. The WT CViia2 neurons treated with gamma-secretase inhibitor DAPT demonstrate nuclear exclusion of KAT5 (E). The statistical significance was analyzed as described in methods section across cells per culture group, with the average for each cell-type shown as a single dot in the plots on the right (F and G). The WT cells are statistically significantly different in nuclear signal intensity than either the APPSWE heterozygous cells (p<0.01), the APP duplication (p<0.05), and PSEN2 N141I heterozygous mutants (p<0.01). The gamma-secretase inhibitor treated cells approached statistical significance (p<0.09).

Journal: bioRxiv

Article Title: Kat5 cKO Biological Domain Signatures Align with Human Alzheimer’s Disease

doi: 10.1101/2025.09.13.676046

Figure Lengend Snippet: Subcellular localization of KAT5 in human iPSC-derived WT and FAD neurons. Induced-pluripotent stem cells (iPSCs) from a WT CViia2 strain, APP Swedish (APPswed) and APP duplication mutants (APPdup, a model of trisomy 21) were differentiated into glutamatergic neurons and stained for KAT5 (green), DAPI (blue) to show nuclear localization and MAP2 (red) to show cytosolic cytoskeletal structure. The wild-type cells demonstrate ubiquitous localization (A) with fluorescent overlap with the DAPI nuclear signal. All explored FAD mutant lines (B and C) and APP duplication lines (D) show specific nuclear exclusion of KAT5. The WT CViia2 neurons treated with gamma-secretase inhibitor DAPT demonstrate nuclear exclusion of KAT5 (E). The statistical significance was analyzed as described in methods section across cells per culture group, with the average for each cell-type shown as a single dot in the plots on the right (F and G). The WT cells are statistically significantly different in nuclear signal intensity than either the APPSWE heterozygous cells (p<0.01), the APP duplication (p<0.05), and PSEN2 N141I heterozygous mutants (p<0.01). The gamma-secretase inhibitor treated cells approached statistical significance (p<0.09).

Article Snippet: A surface object workflow was used in Imaris to define the DAPI+ nuclear ROI.

Techniques: Derivative Assay, Staining, Mutagenesis