Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells
Name
s41467-019-11493-2.pdf
Description
Published version
Size
4.5 MB
Format
Adobe PDF
Checksum (MD5)
d9c7f413ae9ae6ef88dd3cb6ec3fc602
Author(s)
Reitman, Zachary J.
Paolella, Brenton R.
Bergthold, Guillaume
Pelton, Kristine
Becker, Sarah
Jones, Robert
Sinai, Claire E.
Malkin, Hayley
Huang, Ying
Grimmet, Leslie
Date Issued
August 2019
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Reitman, Z.J. et al. Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells. Nature Communications 10, 1 (August 2019): 3731 © 2019 The Author(s)
Version
Final published version
Abstract
Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Broad Institute of MIT and Harvard
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-019-11493-2
