The transcriptomic analysis for Usp18 heterozygous depletion in established AML1/ETO 9a leukemia mouse model [AE9a_RNA-seq]

Usp18 is a potent negative reguator of type I IFN signaling. However, it is not well characterized how Usp18 affects IFN stimulated genes (ISGs) induction in AML in mouse model. Here, we analyzed the transcriptomic data when combined with heterozygous depletion of USP18, which phenotypicaly reduce AE9a leukemia progression. Overall design: Usp18+/f UBCER-Cre AML1/ETO 9a leukemia cells were transplanted into recipient mice. After mice become sick, oil or tamoxifen were injected to heterozygously deplete Usp18. Three days after first injection, Lin- c-kit+ AML cells were sorted from mouse splenocytes. Then performed RNA-sequencing of control (Oil) and USP18KD (Tam) RNA. For RNA-sequencing, 3 biological replicates were prepared for each condition.

Usp18是I型干扰素(type I IFN)信号通路的强效负调控因子。然而，目前尚不明确Usp18如何影响小鼠模型中急性髓系白血病(AML)内干扰素刺激基因(IFN stimulated genes, ISGs)的诱导表达。本研究结合可显著抑制AE9a白血病进展的Usp18杂合缺失模型，对转录组数据展开分析。

实验整体设计如下：将Usp18+/f UBCER-Cre AML1-ETO 9a白血病细胞移植至受体小鼠体内。待小鼠发病后，分别注射玉米油（Oil）或他莫昔芬（tamoxifen）以实现Usp18的杂合敲除。首次给药3天后，从小鼠脾脏淋巴细胞中分选Lin⁻ c-kit⁺ AML细胞，随后对对照组（Oil处理组）与USP18敲低组（Tam处理组）的RNA开展RNA测序(RNA-sequencing)。RNA测序实验中，每组均设置3个生物学重复样本。