RNA sequencing of organoids isolated from pancreatic cancer mouse model KRASG12D; p53R172H; Ptf1a-Cre.. Mus musculus

We studied the transcriptomics of pancreatic ductal adenocarcinoma (PDAC) and the role of a splicing factor called SF3B1 in this context. We generated mice that will develop PDAC via an inducible expression of KRASG12D; p53R172H specifically in the pancreas using a Ptf1a-Cre. Overall design: We have isolated organoids from: KrasG12D; p53R172H (KP), KrasG12D; p53R172H; Ptf1a-Cre (KPC) , KrasG12D; p53R172H; SF3b1 Fl/+ (KPS), and KrasG12D; p53R172H; Ptf1a-Cre; SF3b1 Fl/+ (KPCS) mice. We have 3 organoids per group, representing 3 biological replicates. We have exposed the organoids to normoxia (21% O2) or hypoxia (3%O2).

本研究围绕胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）的转录组学，以及剪接因子SF3B1在该疾病中的功能展开探究。我们通过Ptf1a-Cre重组酶系统，在小鼠胰腺组织中特异性诱导KRASG12D与p53R172H的表达，构建了可自发进展为胰腺导管腺癌的模型小鼠。实验整体设计如下：我们从以下4组小鼠中分离胰腺类器官：KrasG12D; p53R172H（KP组）、KrasG12D; p53R172H; Ptf1a-Cre（KPC组）、KrasG12D; p53R172H; SF3b1 Fl/+（KPS组），以及KrasG12D; p53R172H; Ptf1a-Cre; SF3b1 Fl/+（KPCS组）。每组包含3个类器官样本，对应3次生物学重复。随后我们将各组类器官分别置于常氧（21% O₂）与低氧（3% O₂）环境中进行培养处理。