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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Impaired lipid metabolism in astrocytes underlies degeneration of cortical projection neurons in hereditary spastic paraplegia

Fig. 1

SPG3A mutations in ATL1 result in axonal outgrowth defects in isogenic hPSC lines. a, b Sequencing of genomic ATL1 confirms validity of both homozygous (a; ATL1-A161P #4) and heterozygous clones (b; ATL1-A161P #70). c, d Correction of point mutations in SPG3A iPSCs to generate isogenic WT iPSCs. Sequencing of genomic ATL1 locus in SPG3A patient-derived iPSCs (ATL1-P342S) (c), which is corrected to WT (ATL1-342-Cor) (d). e Representative images of Tau staining (green) assessing axonal outgrowth of cortical PNs in WT, ATL1-P342S, ATL1-342-Cor, H9, ATL1-A161P #70 and ATL1-A161P #4 groups. Ctip2 (red); Hoechst (cyan). Scale bar: 50 µm. f, g Quantification of axonal length in cortical PNs derived from WT, ATL1-P342S, ATL1-342-Cor, H9, ATL1-A161P #70 and ATL1-A161P #4 hPSCs. h Tau staining reveals axonal swellings in WT, ATL1-P342S, ATL1-342-Cor, H9 and ATL1-A161P cortical PNs at 12 weeks after differentiation. Scale bar: 20 µm. i, j Quantification of axonal swellings per 100 µm of axon length in WT, ATL1-P342S, and ATL1-342-Cor, H9 and ATL1-A161P cortical PNs. Data are represented as mean ± SEM from triplicate biological samples. The statistical significance of mean values among three groups was analyzed using ANOVA. *p < 0.05 compared to WT (for ATL1-P342S) and H9 (for ATL1-A161P #70 and #4), respectively; #p < 0.05 compared to ATL1-P342S

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