scholarly journals Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma

2018 ◽  
Author(s):  
Jinzhou Yuan ◽  
Hanna Mendes Levitin ◽  
Veronique Frattini ◽  
Erin C. Bush ◽  
Deborah M. Boyett ◽  
...  
Keyword(s):  
Single Cell ◽  
Glioma Cells ◽  
High Grade Glioma ◽  
Transformed Cells ◽  
High Grade ◽  
Tight Coupling ◽  
Mesenchymal Tumors ◽  
Neural Lineage ◽  
Mesenchymal Transformation ◽  
The Brain

ABSTRACTBackgroundDespite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq.ResultsWhile HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, reminiscent of molecular interactions between glioma and immune cells established in animal models. Additionally, we discovered a tight coupling between lineage resemblance and proliferation among malignantly transformed cells. Glioma cells that resemble oligodendrocyte progenitors, which proliferate in the brain, are often found in the cell cycle. Conversely, glioma cells that resemble astrocytes, neuroblasts, and oligodendrocytes, which are non-proliferative in the brain, are generally non-cycling in tumors.ConclusionsThese studies reveal a relationship between cellular identity and proliferation in HGG and distinct population structures that reflects the extent of neural and non-neural lineage resemblance among malignantly transformed cells.

scholarly journals PDTM-21. MULTI-MODAL PROFILING OF PEDIATRIC HIGH-GRADE GLIOMA SINGLE CELLS USING PATCH-SEQ

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi191-vi191
Author(s):  
Shawn Gillespie ◽  
Marlene Arzt ◽  
Pamelyn Woo ◽  
Michelle Monje
Keyword(s):  
Single Cell ◽  
Single Cells ◽  
Glioma Cells ◽  
High Grade Glioma ◽  
Neural Circuitry ◽  
Extracellular Potassium ◽  
High Grade ◽  
Transcriptional Profiles ◽  
Pediatric High Grade Glioma ◽  
Developmental Hierarchy

Abstract Pediatric and adult high-grade gliomas are characterized by extensive intra-tumoral transcriptional heterogeneity. When measured by single cell RNA sequencing, gliomas reveal themselves as continuums of stemness and differentiation programs with important implications for therapy, but to date this transcriptional information has not been directly linked to physiological behaviors of cells. Recent work from our group establishes the electrical integration of glioma cells into neural circuitry. One subpopulation of glioma cells participates in glutamatergic synaptic communication with neurons, and a distinct subpopulation of cells sense and respond to extracellular potassium flux of neuronal networks by an entirely distinct mechanism. Our data support a model in which both modes of electrical communication are critical to glioma growth, but current associations between the electrophysiological properties of a cell, its transcriptional profile and developmental state are correlational in nature. Patch-seq is needed to clarify the relationship between transcriptional profiles of quiescent/cycling stem-like cells and the observed electrophysiological behaviors. Put more simply, patch-seq will clarify where the synaptically-connected glioma cells exist along a developmental hierarchy. METHODS Here, we adapt a recently described technique called patch-seq to record the electrophysiological profiles of individual pediatric high-grade glioma cells by whole cell patch-clamp and subsequently isolate their mRNA for single cell sequencing by smart-seq2 and analysis using Seurat. In this way, we couple electrophysiological and transcriptomic profiles to unambiguously assign functional identities to cells with transcriptional profiles along a developmental hierarchy. RESULTS We report the successful adaptation of patch-seq for use with patient-derived diffuse intrinsic pontine glioma (DIPG) xenografts in acute brain slice preparations, enabling evaluation of single glioma cells integrated in intact neural circuitry. CONCLUSIONS Data synthesizing the electrophysiological and transcriptomic profiles of single glioma cells in the context of the developmental hierarchy will be presented.

scholarly journals Single-Cell Transcriptomic Analysis Revealed a Critical Role of SPP1/CD44-Mediated Crosstalk Between Macrophages and Cancer Cells in Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong He ◽  
Luoyan Sheng ◽  
Deshen Pan ◽  
Shuai Jiang ◽  
Li Ding ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Heterogeneity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Cell Communication ◽  
High Grade Glioma ◽  
Sequencing Analysis ◽  
High Grade ◽  
Cellular Components

High-grade glioma is one of the most lethal human cancers characterized by extensive tumor heterogeneity. In order to identify cellular and molecular mechanisms that drive tumor heterogeneity of this lethal disease, we performed single-cell RNA sequencing analysis of one high-grade glioma. Accordingly, we analyzed the individual cellular components in the ecosystem of this tumor. We found that tumor-associated macrophages are predominant in the immune microenvironment. Furthermore, we identified five distinct subpopulations of tumor cells, including one cycling, two OPC/NPC-like and two MES-like cell subpopulations. Moreover, we revealed the evolutionary transition from the cycling to OPC/NPC-like and MES-like cells by trajectory analysis. Importantly, we found that SPP1/CD44 interaction plays a critical role in macrophage-mediated activation of MES-like cells by exploring the cell-cell communication among all cellular components in the tumor ecosystem. Finally, we showed that high expression levels of both SPP1 and CD44 correlate with an increased infiltration of macrophages and poor prognosis of glioma patients. Taken together, this study provided a single-cell atlas of one high-grade glioma and revealed a critical role of macrophage-mediated SPP1/CD44 signaling in glioma progression, indicating that the SPP1/CD44 axis is a potential target for glioma treatment.

In Vitro Evaluation of Iodine-125-Labeled Monoclonal Antibody (MAb 425) in Human High-Grade Glioma Cells

1996 ◽  
Vol 19 (6) ◽  
pp. 601-608 ◽  
Author(s):  
Jacqueline G. Emrich ◽  
Hans Bender ◽  
Reiner Class ◽  
Jeffrey Eshleman ◽  
Curtis Miyamoto ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Glioma Cells ◽  
High Grade Glioma ◽  
High Grade ◽  
In Vitro Evaluation ◽  
Iodine 125

scholarly journals P11.49 An electrophysiological signature of glioma infiltration in the ex vivo human brain

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii54-iii54
Author(s):  
A J Kirby ◽  
J P Lavrador ◽  
C Brogna ◽  
F Vergani ◽  
C Chandler ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Brain Slices ◽  
Glioma Cells ◽  
Low Grade ◽  
Tissue Preparation ◽  
High Grade ◽  
Spontaneous Seizure ◽  
Human Brain Tissue ◽  
The Brain

Abstract BACKGROUND Invading glioma cells affect the physiological function of the peritumoural cortex. This may manifest clinically as seizures. Here, we investigate the effect the invading glioma cells on the electrophysiological signalling of the peritumoral cortex using living human brain tissue donated by people having a craniotomy for glioma resection (REC approval, 18/SW/002). MATERIAL AND METHODS The brain tissue was cut into thin slices, which preserved the architecture of the glioma and the adjacent healthy brain. The brain slices were incubated in 5-aminolevulinic acid to make the glioma cells fluorescent. We observed 5-ALA induced fluorescence in both low-grade and high-grade gliomas. This enabled us to make electrophysiological recordings of brain activity across the boundary between glioma and brain. RESULTS We recorded from brain slices of 5 participants with glioblastoma and 4 participants with oligodendroglioma (WHO grade II - III). Spontaneous “seizure-like” discharges were recorded in brain slices from 5/8 participants (3 GBM, 2 oligodendroglioma) who reported seizures and from one participant (GBM) who had not had any clinical seizures. Further analysis of the electrical discharges revealed that they could be subdivided into two distinct types based on the major frequencies in the discharge. CONCLUSION We concluded that human brain slices from people with either a low-grade or a high-grade glioma can generate spontaneous seizure-like discharges. This electrophysiological signature will be compared to infiltration and grade of the glioma cells in the donated sample. The living human brain tissue preparation gives us a platform to study the mechanisms of tumour-associated seizures and how abnormal neural activity affects glioma growth.

scholarly journals PO-334 Identification of shared lineage programs across high-grade glioma subtypes by single-cell RNA-seq

2018 ◽  
Author(s):  
S Muller ◽  
E Di Lullo ◽  
A Bhaduri ◽  
M Aghi ◽  
AR Kriegstein ◽  
...  
Keyword(s):  
Single Cell ◽  
High Grade Glioma ◽  
High Grade ◽  
Rna Seq

scholarly journals Dose distribution of the brain tissue associated with cognitive functions in high-grade glioma patients

2020 ◽  
Vol 24 (1) ◽  
pp. 1-10
Author(s):  
J. Jacob ◽  
E. Clausse ◽  
M.A. Benadjaoud ◽  
C. Jenny ◽  
M. Ribeiro ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Cognitive Functions ◽  
Dose Distribution ◽  
High Grade Glioma ◽  
High Grade ◽  
The Brain

scholarly journals First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma

2020 ◽  
Vol 26 (8) ◽  
pp. 1820-1828 ◽  
Author(s):  
Patrick Y. Wen ◽  
Timothy F. Cloughesy ◽  
Alan G. Olivero ◽  
Kari M. Morrissey ◽  
Timothy R. Wilson ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Mtor Inhibitor ◽  
High Grade Glioma ◽  
High Grade ◽  
The Brain
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