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Genome Med. 2018 Jul 24;10(1):57. doi: 10.1186/s13073-018-0567-9.

Single-cell transcriptome analysis of lineage diversity in high-grade glioma.

Author information

1
Department of Systems Biology, Columbia University Medical Center, New York, NY, 10032, USA.
2
Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA.
3
Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY, 10032, USA.
4
Department of Neurological Surgery, Columbia University Medical Center, New York, NY, 10032, USA.
5
Department of Science and Technology, Università degli Studi del Sannio, 82100, Benevento, Italy.
6
Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
7
Department of Pediatrics, Columbia University Medical Center, New York, NY, 10032, USA.
8
Department of Neurology, Columbia University Medical Center, New York, NY, 10032, USA.
9
Department of Systems Biology, Columbia University Medical Center, New York, NY, 10032, USA. pas2182@cumc.columbia.edu.
10
Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY, 10032, USA. pas2182@cumc.columbia.edu.
11
Department of Biochemistry & Molecular Biophysics, Columbia University Medical Center, New York, NY, 10032, USA. pas2182@cumc.columbia.edu.

Abstract

BACKGROUND:

Despite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs).

METHODS:

We sampled the cellular milieu of HGGs by profiling dissociated human surgical specimens with a high-density microwell system for massively parallel single-cell RNA-Seq. We analyzed the resulting profiles to identify subpopulations of both HGG and microenvironmental cells and applied graph-based methods to infer structural features of the malignantly transformed populations.

RESULTS:

While 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.

CONCLUSIONS:

These 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.

PMID:
30041684
PMCID:
PMC6058390
DOI:
10.1186/s13073-018-0567-9
[Indexed for MEDLINE]
Free PMC Article

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