Extended Data Fig. 5: mtDNA-dependent ISG response in Mgme1−/− cells.
From: Ribonucleotide incorporation into mitochondrial DNA drives inflammation
a, Agglomerative heat map showing the distribution of mRNA ISGs intensities in wild-type immortalized MEFs either left untreated or treated with 40 µM ddC and indicated siRNA for 72 h (left panel). Z-score intensities were calculated and clustering was performed using the Euclidean distance metric and the ‘average’ method (left panel). Heat map (log2 fold change, decreasing order) of ISGs mRNA profiles in wild-type immortalized MEFs treated with the indicated siRNA for 72 h (right panel). Asterisks mark ISGs whose expression was significantly altered between siMgme1 and siMgme1; ddC (n = 3 biologically independent experiments). *q < 0.05; **q < 0.01, ***q < 0.001. b, RT-qPCR analysis of mtDNA levels in wild-type immortalized MEFs either left untreated or treated with 40 µM ddC and indicated siRNA for 72 h. mtDNA levels were monitored with probes for D loop, cytochrome b (CytB) and non-NUMT. n = 3 biologically independent experiments. c, ISG expression and mtDNA levels in Mgme1+/+ and Mgme1−/− immortalized MEFs treated with 40 µM ddC for 6 days. n = 3 biologically independent experiments. P values were calculated using unpaired two-tailed Student t-test (a), two-way ANOVA with Tukey’s multiple comparison test (b) or one-way ANOVA with Tukey’s multiple comparison test (c). data are presented as mean ± SD. *q < 0.05, **q < 0.01, ***q < 0.001 (a).
