Fig. 1: Endogenous remyelination fails to restore the oligodendrocyte population after moderate or severe demyelination.

A Experimental timeline. Untreated and vehicle-treated mice were used to study endogenous remyelination. B Mobp-EGFP mice underwent longitudinal in vivo two-photon imaging of OLs in V1. C Cranial window placement above V1. D Representative images of V1 OLs in one mouse at baseline (-3.5 weeks), end of cuprizone (0 weeks), and during remyelination (1.5 and 7 weeks). Lost OLs (dark blue) and new OLs (light blue) are encircled. E Cumulative OL loss and gain (as a percentage of baseline OLs) in individual mice over time (n = 15). F Three parameter Gompertz growth curve (95% CI) fit to group cumulative OL loss and gain shown for visualization. Statistical comparisons performed on parameters derived from three parameter growth curves fit to individual mice (Supplementary Fig. 4A, B). Maximum growth rate occurred earlier for loss than gain. Gain asymptote is lower than loss asymptote. G Cumulative OL gain and cumulative OL loss are tightly correlated at 7 weeks. H At <50% OL loss, mice make as many new OLs as they lose by 7 weeks. At ≥50% OL loss, mice make fewer new OLs than they lose. I OL number (as a percentage of baseline OLs) in individual mice over time (n = 15). Dashed line at 100%. J OL number and cumulative OL loss are tightly correlated at 7 weeks. Dashed line at 100%. In (F), Max. growth rate: paired t test (t(14) = 10.12, ***p < 0.0001, n = 15). Asymptote: paired t test (t(14) = 3.64, **p = 0.0027, n = 15). In (G), linear regression (F(1, 8) = 23.79, n = 10). In (H) < 50% loss, paired t test (t(3) = 1.87, p = 0.16, n = 4). In H ≥ 50% loss, paired t test (t(5) = 5.40, **p = 0.0029, n = 6). In (J), linear regression (F(1, 8) = 33.06, n = 10). n.s. not significant, **p < 0.01, ***p < 0.001; line of best fit ± 95% CI in (G, J); n=mice; two-sided statistical tests. See Supplementary Data 1 for statistical details and Source Data file for source data. OL = oligodendrocyte, V1 = primary visual cortex.