Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver -bulk RNA-seq

ADAR1 is thought to be an immune suppressor maintaining self-tolerance to endogenous nucleic acids. Lack of ADAR1 results in MDA5 (Ifih1) activation and MDA5 deletion rescues ADAR1 null embryonic lethality. We generated liver specific ADAR1; MDA5 double KO mice and performed high throughput sequencing to investigate hepatic inflammation in these mice. Bulk RNA was sequenced on the HiSeq X platform. Over 100 million pairs of mappable reads for each sample were obtained. Transcriptomes of Ifih1-/- Adar1wt/wt Alb-Cre+ (n=3), Ifih1-/- Adar1wt/flox Alb-Cre+ (n=2), and Ifih1-/- Adar1flox/flox Alb-Cre+ (n=2) mice livers were compared to examine the effects of Adar1 depletion against Ifih1 null background.RNA腺苷脱氨酶1（ADAR1）被认为是一类免疫抑制因子，可维持机体对内源核酸的自身耐受。ADAR1缺失会导致黑色素瘤分化相关蛋白5（MDA5, Ifih1）激活，而MDA5敲除可挽救ADAR1敲除小鼠的胚胎致死表型。我们构建了肝脏特异性ADAR1与MDA5双敲除小鼠，并通过高通量测序技术探究此类小鼠的肝脏炎症情况。批量RNA（bulk RNA）样本在HiSeq X测序平台上完成测序，每个样本均可获得超过1亿对可比对读段。我们对三类小鼠的肝脏转录组进行了比较分析：Ifih1-/- Adar1wt/wt Alb-Cre+（n=3）、Ifih1-/- Adar1wt/flox Alb-Cre+（n=2）以及Ifih1-/- Adar1flox/flox Alb-Cre+（n=2），以探究在Ifih1缺失背景下ADAR1耗竭的生物学效应。