Fig. 4. Impact of ZNF417/587 on neuronal differentiation, function, and homeostasis.
(A) Number of DE elements in indicated cells. (B) Expression in KD (left) or HERVK-silenced (right) versus control iN of genes classified with Allen Brain Atlas Gene Ontologies (GOs) compared to random genes (P values, Wilcoxon test). (C) Examples of DE genes related to GABAergic pathway. (D) HERVK with (top) RNA-seqs of control versus KD and (middle) control versus HERVK-CRISPRi iN, and (bottom) KZFPs ChIP-seqs in hESC. (E) Western blot of NCCIT cell lysates probed with anti-ENV or anti-actin antibodies. (F) Expression of ISG (with fold change > 5 in IFN-treated normal tissues or cells according to the Interferome database) in KD versus control iN. In red, DE ISG (fold change > 2, FDR < 0.05). Venn diagram indicates number of DE genes stimulated by each IFN type. (G) Fold change expression of antiviral ISG in indicated conditions versus control iN (ND, not detected). (H) Forty-three–day organoids, with size quantification underneath (P values, Mann Whitney U test). (I) PAX6 immunostaining and RT-qPCR quantification (P values, two-tailed t test), and (J) fold change expression of neuronal function–related genes and (K) ISG in 20-day organoids. Independent duplicates (A to G) or triplicates (D, J, and K) were used. Error bars represent the SD (***FDR < 0.001, **FDR < 0.01, and *FDR < 0.05).