Research Papers:

Systematic characterization of lncRNAs’ cell-to-cell expression heterogeneity in glioblastoma cells

Dekang Lv _, Xiang Wang, Jun Dong, Yan Zhuang, Shuyu Huang, Peter C.K. Leung, Puxiang Chen, Xiaodong Li, Bo Zhang, Zhiguang Li and Bilian Jin

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Oncotarget. 2016; 7:18403-18414. https://doi.org/10.18632/oncotarget.7580

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Dekang Lv1,*, Xiang Wang1,*, Jun Dong1, Yan Zhuang1, Shuyu Huang1, Binbin Ma2, Puxiang Chen3, Xiaodong Li1, Bo Zhang2, Zhiguang Li1, Bilian Jin1

1Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China

2Department of Neurosurgery, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, P.R. China

3Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Xiang Wang, e-mail: wangx6281@dmu.edu.cn

Zhiguang Li, e-mail: zhiguangli@dmu.edu.cn

Bilian Jin, e-mail: jinbilian@dmu.edu.cn

Keywords: GBM, lncRNA, heterogeneity, single-cell RNA-seq, self-organizing map

Received: November 11, 2015    Accepted: February 11, 2016    Published: February 23, 2016


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.

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