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. 2018 Aug 14;115(35):E8246–E8255. doi: 10.1073/pnas.1802620115

Fig. 5.

Fig. 5.

Chd7 promotes OPC survival through p53 down-regulation. (A) Immunostaining of Casp3 and PDGFRα in the CC of P7 iKO mice. (Scale bar, 10 μm.) (B) Quantification of Casp3+ OPCs as a percentage of OPCs in P7 Ctrl and iKO mice. Data are presented as mean ± SEM (n = 3 Ctrl and 4 iKO). (C) Barplot representing the LogFC of Trp53 and p53 target-genes involved in apoptosis pathway (red), cell-cycle arrest (orange), or DNA repair (yellow) between iKO and Ctrl mice. Dashed gray line represents FC = 1.2 (n = 7 Ctrl and 5 iKO). (D) Immunostaining of p53 and PDGFRα in the CC from P7 Ctrl and iKO mice. (Scale bars, 10 μm.) (E and F) Quantification of p53+ OPCs (nb/mm2, E) or as a percentage of OPCs (F) in the CC and Ctx of P7 Ctrl and iKO mice. Data are presented as mean ± SEM (n = 3 Ctrl and 4 iKO). (G) Quantification of MCM2+ and MCM2− cells as a percentage of total p53+ cells in the CC of iKO P7 mice. Data are presented as mean ± SEM (n = 3 Ctrl and 4 iKO). (H) Representative tracks for Trp53 locus integrating: (i) ChIP-seq data for Olig2 and Sox10, Chd7, and Chd8 in OPCs and; (ii) ATAC data from Ctrl and iKO P7 OPCs. (I, Left) Diagram representing tamoxifen (Tam) administration at P1 and P4 and PFT injection at P3, P4, and P5 followed by tissue collection at P7. (Right) Immunostaining of PDGFRα in the CC from P7 Ctrl, iKO and iKO+PFT mice. (Scale bars, 10 μm.) (J) Quantification of p53+ cells as a percentage of OPCs in the CC of P7 Ctrl, iKO, Ctrl+PFT, and iKO+PFT mice. Data are presented as mean ± SEM (n = 3 Ctrl, 4 iKO, 3 Ctrl+PFT and 3 iKO+PFT). (K) Quantification of PDGFRα+ cells (nb/mm2) in the CC of P7 Ctrl, iKO, Ctrl+PFT and iKO+PFT mice. Data are presented as mean ± SEM (n= 5 Ctrl, 5 iKO, 3 Ctrl+PFT and 3 iKO+PFT). (L) Quantification of MCM2+ cells as a percentage of OPCs in the CC of P7 Ctrl+PFT and iKO+PFT mice. Data are presented as mean ± SEM (n = 3). (M) Scheme representing Chd7 function in OPC survival. Proliferative OPCs (light blue), noncycling OPCs (blue) in Ctrl, iKO, and iKO+PFT mice. Exact P values can be found in Dataset S2. *P < 0.05, **P < 0.01, and ***P < 0.001.