Genomic heterogeneity in pancreatic cancer organoids and its stability with culture.
Genomic heterogeneity in pancreatic cancer organoids and its stability with culture.
复制标题
DOI：
10.1038/s41525-022-00342-9
复制
发表时间：
2022-12-19
影响因子：
5.3
通讯作者：
Irianto, Jerome
中科院分区：
文献类型：
--
作者：
Usman, Olalekan H.;Zhang, Liting;Xie, Gengqiang;Kocher, Hemant M.;Hwang, Chang-il;Wang, Yue Julia;Mallory, Xian;Irianto, Jerome
近年来，源自患者的胰腺癌类器官培养的建立为研究人员创造了一个令人兴奋的机会，可以在密切再现肿瘤的模型上进行广泛的体外研究。胰腺癌生物学中的突出问题之一是在疾病中观察到的基因组异质性的原因和后果。然而，为了使用胰腺癌类器官作为研究基因组变异的模型，我们需要首先了解基因组异质性的程度及其在类器官内的稳定性。在这里，我们使用单细胞全基因组测序来研究两个独立的胰腺癌类器官系的基因组异质性，以及它们在扩展培养中的基因组稳定性。在类器官中观察到具有相似拷贝数特征的克隆群体，并且这些克隆的比例随着培养的扩展而发生变化，这表明一些克隆的生长优势。然而，在每个克隆群体中也观察到亚克隆基因组异质性，表明胰腺癌细胞本身的基因组不稳定性。此外，我们的转录组分析还揭示了拷贝数改变与基因表达调控之间的正相关性，表明这些拷贝数改变的“基因剂量”效应转化为基因表达调控。
The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. One of the outstanding question in pancreatic cancer biology is the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoid lines, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.
登录
查看更多内容
影响因子：
48
作者：
Dong X;Zhang L;Milholland B;Lee M;Maslov AY;Wang T;Vijg J
通讯作者：
Vijg J
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
Huang, Ling;Holtzinger, Audrey;Muthuswamy, Senthil K.
通讯作者：
Muthuswamy, Senthil K.
影响因子：
46.9
作者：
Gao R;Bai S;Henderson YC;Lin Y;Schalck A;Yan Y;Kumar T;Hu M;Sei E;Davis A;Wang F;Shaitelman SF;Wang JR;Chen K;Moulder S;Lai SY;Navin NE
通讯作者：
Navin NE
DNA损伤遵循修复因子耗竭，并预测孔迁移后癌细胞的基因组变异。
DOI：
10.1016/j.cub.2016.11.049
发表时间：
2017-01-23
期刊：
Current biology : CB
影响因子：
--
作者：
Irianto J;Xia Y;Pfeifer CR;Athirasala A;Ji J;Alvey C;Tewari M;Bennett RR;Harding SM;Liu AJ;Greenberg RA;Discher DE
通讯作者：
Discher DE