小柯机器人

单细胞图谱显示肿瘤间和肿瘤内异质性的不同保留
2022-03-20 16:24

加拿大英属哥伦比亚大学Marco A. Marra研究小组的最新工作表明,原发性胶质母细胞瘤和相匹配的外植体和细胞系的单细胞图谱显示出肿瘤间和肿瘤内异质性的不同保留。这一研究成果于2022年3月17日在线发表在国际学术期刊《癌细胞》上。

研究人员分析了12个IDH野生型胶质母细胞瘤(GBM)(包括两个复发的肿瘤)的批量外显子和单细胞基因组和转录组谱,以及来自这些肿瘤的患者衍生外植体(PDE)和胶质瘤(GS)系。研究人员发现,PDE在基因上与它们的母体肿瘤相似,并不同程度地保留了基因表达特征。值得注意的是,与它们的母体肿瘤相比,PDE似乎表现出类似的转录异质性水平,而GS系往往富含转录状态更均匀的细胞。这里介绍的方法和数据集将提供一个宝贵的资源,帮助指导使用GBM衍生模型的实验,特别是在研究细胞异质性方面。

据介绍,GBM是一种侵袭性脑肿瘤,其特点是广泛的瘤间和瘤内异质性。最近,患者衍生的模型,如类器官和外植体,已成为研究这种异质性的有用模型,尽管它们能在多大程度上再现GBM的基因组特征仍不清楚。

附:英文原文

Title: Single-cell landscapes of primary glioblastomas and matched explants and cell lines show variable retention of inter- and intratumor heterogeneity

Author: Véronique G. LeBlanc, Diane L. Trinh, Shaghayegh Aslanpour, Martha Hughes, Dorothea Livingstone, Dan Jin, Bo Young Ahn, Michael D. Blough, J. Gregory Cairncross, Jennifer A. Chan, John J.P. Kelly, Marco A. Marra

Issue&Volume: 2022-03-17

Abstract: Glioblastomas (GBMs) are aggressive brain tumors characterized by extensive inter- and intratumor heterogeneity. Patient-derived models, such as organoids and explants, have recently emerged as useful models to study such heterogeneity, although the extent to which they can recapitulate GBM genomic features remains unclear. Here, we analyze bulk exome and single-cell genome and transcriptome profiles of 12 IDH wild-type GBMs, including two recurrent tumors, and of patient-derived explants (PDEs) and gliomasphere (GS) lines derived from these tumors. We find that PDEs are genetically similar to, and variably retain gene expression characteristics of, their parent tumors. Notably, PDEs appear to exhibit similar levels of transcriptional heterogeneity compared with their parent tumors, whereas GS lines tend to be enriched for cells in a more uniform transcriptional state. The approaches and datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived models, especially in the context of studying cellular heterogeneity.

DOI: 10.1016/j.ccell.2022.02.016

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00068-X

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx


本期文章:《癌细胞》:Online/在线发表

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