An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity
An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity
复制标题
DOI：
10.1038/s41467-020-15155-6
复制
发表时间：
2020-03-11
影响因子：
16.6
通讯作者：
Drost, Jarno
中科院分区：
文献类型：
--
作者：
Calandrini, Camilla;Schutgens, Frans;Drost, Jarno
肾肿瘤是儿童最常见的实体肿瘤之一，由不同的亚型组成，在许多方面都不同，包括细胞起源、遗传学和病理学。目前缺乏捕捉疾病异质性的临床前细胞模型。在这里，我们介绍了第一个儿科癌症有机生物库。它包含来自50多名患有不同亚型肾癌的儿童的肿瘤和匹配的正常肾器官，包括肾母细胞瘤、恶性横纹肌样瘤、肾细胞癌和先天性中胚层肾瘤。儿科肾肿瘤有机化合物保留了天然肿瘤的关键特性，有助于揭示患者特定的药物敏感性。利用单细胞RNA测序和高分辨率3D成像，我们进一步证明了来自Wilms肿瘤的器官样培养物由多种不同的细胞类型组成，包括上皮细胞、间质细胞和胚泡样细胞。我们的有机生物库捕捉了儿童肾脏肿瘤的异质性，为基础癌症研究、药物筛选和个性化药物提供了具有代表性的模型集合。临床前细胞培养模型捕捉儿童肾脏肿瘤的异质性是有限的。在这里，作者建立和描述了肿瘤的有机生物库和来自50多名患有不同亚型肾癌的儿童的匹配的正常有机培养。
Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine.Pre-clinical cell culture models capturing the heterogeneity of childhood kidney tumours are limited. Here, the authors establish and characterise an organoid biobank of tumour and matched normal organoid cultures from over 50 children with different subtypes of kidney cancer.