Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells
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; Herbert, Zachary T.; Sun, Yu; Weatherbee, Jessica L.; Alberta, John A.; Daley, John F.; Rozenblatt-Rosen, Orit; Condurat, Alexandra L.; Qian, Kenin; Khadka, Prasidda; Segal, Rosalind A.; Haas-Kogan, Daphne; Filbin, Mariella G.; Suva, Mario L.; Regev, Aviv; Stiles, Charles D.; Kieran, Mark W.; Goumnerova, Liliana; Ligon, Keith L.; Shalek, Alexander K; Bandopadhayay, Pratiti; Beroukhim, Rameen; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Institute for Medical Engineering and Science; Massachusetts Institute of Technology. Department of Chemistry; David H. Koch Institute for Integrative Cancer Research at MIT; Broad Institute of MIT and Harvard
Springer Science and Business Media LLC
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)
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