Fig. 7: Neuronal vulnerability is distinct from astroglial stress and is partially rescuable in C9 CO slices. | Nature Neuroscience

Fig. 7: Neuronal vulnerability is distinct from astroglial stress and is partially rescuable in C9 CO slices.

From: Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology

Fig. 7

a, Left: representative confocal microscopy images showing γ-H2AX+ foci (arrowheads) in CTIP+ DLNs and SOX9+ astroglial nuclei in C9-L1 (240 DIV) and in C9-L2 CO slices (200 DIV) immersed in medium and treated with GSK or vehicle in comparison to age-matched untreated H-L1 or ISO-L2 control CO slices, respectively. Right: schematic (upper) of the section sampling across the vertical axis of CO slices for quantification (lower). Data represent foci numbers per cell and expressed as the mean ± s.e.m. of section averages; for DLNs, n = 28, 36, 30 sections from 7 control, 8 C9 and 6 GSK-treated C9 independent CO slices, respectively (including 6 independent untreated–treated C9 CO slice-pairs); for astroglia n = 33, 36, 29 from 8 control, 8 C9 and 6 GSK treated C9 independent CO slices, respectively (including 6 independent untreated–treated C9 CO slice-pairs); one-way ANOVA and Tukey’s post hoc test (for astroglia, overall ANOVA P value is indicated in the graph). b, Immunofluorescence confocal stack images (left) displaying pyknosis (arrowheads) in CTIP2+ DLNs and SOX9+ astroglial nuclei in C9-L1 (240 DIV) and in C9-L2 CO slices (200 DIV) treated with GSK or vehicle in comparison to age-matched untreated H-L1 or ISO-L2 control CO slices, respectively, and quantification (right). Data represent the proportion of pyknotic nuclei with residual CTIP2 or SOX9 immunoreactivity and expressed as the mean ± s.e.m.; n = 6 for independent control slices, and 6 independent untreated and GSK-treated C9 CO slice-pairs; one-way ANOVA and Tukey’s post hoc test (for astroglia, overall P value is indicated in the graph). Scale bars, 5 μm (a,b (inset)) or 10 μm (b). See Supplementary Table 3 for detailed statistics.

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