Systematic characterization of lncRNAs' cell-to-cell expression heterogeneity in glioblastoma cells.
Systematic characterization of lncRNAs' cell-to-cell expression heterogeneity in glioblastoma cells.
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胶质母细胞瘤细胞中 lncRNA 细胞间表达异质性的系统表征。
DOI：
10.18632/oncotarget.7580
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发表时间：
2016-04-05
期刊：
影响因子：
--
通讯作者：
Jin B
中科院分区：
文献类型：
--
作者：
Lv D;Wang X;Dong J;Zhuang Y;Huang S;Ma B;Chen P;Li X;Zhang B;Li Z;Jin B
胶质母细胞瘤（GBM）是最常见的恶性成人脑肿瘤，通常与高水平的细胞异质性和不良预后相关。长非编码 RNA (lncRNA) 正在成为肿瘤发生的新型介质。最近开发的单细胞 RNA-seq 为分析 lncRNA 表达谱的细胞间变异性提供了前所未有的方法。在这里，我们全面检查了来自 5 个原代 GBM 和两个胶质母细胞瘤干细胞样细胞 (GSC) 系的 380 个细胞中 2,003 个 lncRNA 的表达模式。利用自组织图谱，我们展示了单个细胞的 lncRNA 表达动态图谱。进一步的分析揭示了 lncRNA 丰度和剪接模式的异质性。此外，lncRNA表达变异也普遍存在于由看似相同的细胞组成的已建立的GSC系中。通过对 GSC 和相应分化细胞培养物的比较分析，我们通过 31 个差异表达的 lncRNA 定义了干性特征，它可以揭示 5 个肿瘤的干性梯度。此外，根据已知的分子亚型分类器 lncRNA，发现每个肿瘤包含代表四种亚型的单个细胞。我们对lncRNA表达异质性的系统表征为未来进一步了解lncRNA的功能、开发有价值的生物标志物和增强GBM生物学知识奠定了基础。
Glioblastoma (GBM) is the most common malignant adult brain tumor generally associated with high level of cellular heterogeneity and a dismal prognosis. Long noncoding RNAs (lncRNAs) are emerging as novel mediators of tumorigenesis. Recently developed single-cell RNA-seq provides an unprecedented way for analysis of the cell-to-cell variability in lncRNA expression profiles. Here we comprehensively examined the expression patterns of 2,003 lncRNAs in 380 cells from five primary GBMs and two glioblastoma stem-like cell (GSC) lines. Employing the self-organizing maps, we displayed the landscape of the lncRNA expression dynamics for individual cells. Further analyses revealed heterogeneous nature of lncRNA in abundance and splicing patterns. Moreover, lncRNA expression variation is also ubiquitously present in the established GSC lines composed of seemingly identical cells. Through comparative analysis of GSC and corresponding differentiated cell cultures, we defined a stemness signature by the set of 31 differentially expressed lncRNAs, which can disclose stemness gradients in five tumors. Additionally, based on known classifier lncRNAs for molecular subtypes, each tumor was found to comprise individual cells representing four subtypes. Our systematic characterization of lncRNA expression heterogeneity lays the foundation for future efforts to further understand the function of lncRNA, develop valuable biomarkers, and enhance knowledge of GBM biology.