Extended Data Fig. 10: Layer-dependent differences in the temporal dynamics of cuprizone-induced loss and regeneration.
a-e) Related to Fig. 7. a) OL population replacement (%) plotted over weekly time bins following cuprizone cessation for each anatomically defined region. Replacement rate is increased from healthy baseline from 2–4 weeks post-cuprizone in L1-3 and CC, and 3–4 weeks post-cuprizone in L4 and L5-6 (Kruskal-Wallis test followed by Steel method for comparison with control, p = 0.034 for L1-3, Weeks 2–4 vs. Healthy; p = 0.034 for L4 Weeks 3–4 vs. Healthy; p = 0.034 for L5-6, Weeks 3–4 vs. Healthy; p = 0.034 for CC Weeks 2–4 vs. Healthy). n = 6 mice (cuprizone), 2 mice were imaged at an extra time point during Week 6. b) First-derivative of the modeled growth curves for healthy baseline and OL replacement (Mechanistic Growth, Gompertz 3P, respectively) showing the response duration of regeneration across regions. c) The regeneration response duration, calculated as the full width at half maximum of the rate curves in (b), is significantly longer in the superficial layers 1–3 compared to the CC (One-way ANOVA followed by Tukey’s HSD, p = 0.048). d) The magnitude of the regeneration response, as calculated by the area under the curve above the healthy baseline rate, is significantly suppressed in L5-6 compared to the CC (One-way ANOVA followed by Tukey’s HSD, p = 0.037). e, f) No significant differences in the duration or magnitude of the cuprizone cell loss response across regions. Data in (a) were calculated based on the raw % change in cell population from baseline. Data in b-f were derived from the modeled and scaled growth curves. n = 6 mice (cuprizone), n = 6 mice (healthy). *p < 0.05, **p < 0.01, n.s. = not significant; for growth curves, cubic splines approximate the measure of center and error bars are 95% confidence intervals; box plots represent the median, interquartile ranges and minimum/maximum values. For detailed statistics, see Supplementary Table 3.
