title: Systematic characterization of lncRNAs' cell-to-cell expression heterogeneity in glioblastoma cells.
abstract: 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.
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Dekang
authors.initials: D
authors.lastname: Lv
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, P.R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, P.R. China.
authors.forename: Puxiang
authors.initials: P
authors.lastname: Chen
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R. China.
authors.forename: Bilian
authors.initials: B
authors.lastname: Jin
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018740:Genetic Heterogeneity; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding
keywords: GBM; heterogeneity; lncRNA; self-organizing map; single-cell RNA-seq