Fig. 3: Sulf2 deletion results in improved oligodendrocyte recruitment and differentiation and is upregulated in chronic active MS lesions.

Tamoxifen-dependent OPC-specific ablation of either Sulf1, Sulf2 alone, or both Sulf1/2 in NG2⁺ OPCs was initiated prior to demyelination. Control animals (lacking cre) were treated in an identical manner. Widefield immunofluorescence for Olig2 (green) and CC1 (red) at 7 d.p.l. (a–d). The density (cells/mm²) of Olig2⁺ oligodendrocytes lineage cells (e), Olig2⁺CC1⁺ postmitotic oligodendrocytes (f) and percentage of CC1⁺ oligodendrocytes (g) was quantified (n = 5 for each group except n = 6 for Sulf1/2 cKO). Mean ± SEM is shown. Two-way ANOVA for Sulf1 and Sulf2 genotypes. Holm–Sidak post-test vs. wild-type control *, **, ***, and *** indicates p < 0.05, 0.01, 0.001, and 0.0001, respectively. h–j Human primary OPCs infected with lentiviral SULF2 knockdown (KD) or scrambled control cultured in mitogen-free conditions for 4 days. Oligodendrocyte differentiation assessed by O4 immunocytochemistry (green) and DAPI (blue) (h, i). j SULF2 KD accelerated O4⁺ oligodendrocyte differentiation (****p < 0.0001 paired t test, n = 6 fetal human samples). k PLP1 immunohistochemistry of chronic active human MS lesion and surrounding normal white matter (NAWM). l RNAscope for PLP1 mRNA in NAWM (pink box in k). m–p Confocal-based RNAscope in situ hybridization at lesion border (black box in k) for SULF2 (green), PDGFRA (red, n), and PLP1 (red, p) mRNA. Arrow represents colocalization of SULF2 with PDGFRA and PLP1 mRNAs. Scale: 20 µm (a–d, m–p), and 50 µm (i, j).