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. 2022 Mar 21;11:e75230. doi: 10.7554/eLife.75230

Figure 1. Oligodendrocyte precursor cells (OPCs) require TDP-43 for survival.

(A) Schematics of CreER activation. At P90, tamoxifen was administered for five consecutive days. Tissue samples were collected 14, 30, and 60 days after the last day of tamoxifen injection. (B) Pdgfra-CreER;RCE allows labeling of oligodendrocyte lineage cells. Yellow arrowheads indicate EGFP+NG2+ OPCs whereas blue arrowheads indicate EGFP+NG2− oligodendrocytes. (C) NG2 staining shows that there is a regional progression in OPC degeneration from white matter to gray matter. The dotted line separates the corpus callosum from cortex. i, ii, and iii regions are zoomed in in D. (D) Region i shows the corpus callosum with a near complete loss of OPCs at P90 + 14. ii shows loss of OPCs in the cortex at P90 + 30. iii shows highly polarized OPCs migrating from the corpus callosum up to cortex. (E) Quantification of NG2+ OPC density in corpus callosum and cortex at 14, 30, and 60 days post injection of tamoxifen (dpi). Statistical significance was determined using one-way ANOVA with Tukey’s multiple comparisons test (n = 4, ***p value < 0.001, n.s. p value >0.05). (F) Ki-67+NG2 + proliferating OPCs increase in number at P90 + 60 in the corpus callosum of PDGFRα-TDP43 KO.

Figure 1.

Figure 1—figure supplement 1. PDGFRα-TDP43 cKO shows a regional difference in degeneration of oligodendrocyte precursor cells (OPCs).

Figure 1—figure supplement 1.

(A) Quantification of NG2+Ki-67+ proliferating OPCs in Figure 1F (unpaired, two-tailed Student’s t-test, ***p value = 0.0002, n = 3,2). (B) Coronal brain sections immunostained for GFAP at 30 and 60 days after tamoxifen injection in PDGFRα-TDP43 Control and cKO. (C) Genetic deletion of Tardbp in old, 6-month-old PDGFRα-TDP43 cKO induces OPC degeneration in the corpus callosum at 14 dpi (similar to Figure 1E). (D) Coronal brain sections immunostained for EGFP, NG2, and PDGFRα at 30 days after tamoxifen injection in PDGFRα-TDP43 Control and cKO. Upon Cre recombination, EGFP+NG2+PDGFRα+ OPCs undergo degeneration.