You are here

Nat Commun DOI:10.1038/s41467-019-11493-2

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Publication TypeJournal Article
Year of Publication2019
AuthorsReitman, ZJ, Paolella, BR, Bergthold, G, Pelton, K, Becker, S, Jones, R, Sinai, CE, Malkin, H, Huang, Y, Grimmet, L, Herbert, ZT, Sun, Y, Weatherbee, JL, Alberta, JA, Daley, JF, Rozenblatt-Rosen, O, Condurat, AL, Qian, K, Khadka, P, Segal, RA, Haas-Kogan, D, Filbin, MG, Suvà, ML, Regev, A, Stiles, CD, Kieran, MW, Goumnerova, L, Ligon, KL, Shalek, AK, Bandopadhayay, P, Beroukhim, R
JournalNat Commun
Volume10
Issue1
Pages3731
Date Published2019 Aug 19
ISSN2041-1723
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.

DOI10.1038/s41467-019-11493-2
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31427603?dopt=Abstract

Alternate JournalNat Commun
PubMed ID31427603
PubMed Central IDPMC6700116
Grant ListRM1 HG006193 / HG / NHGRI NIH HHS / United States
P01 AI039671 / AI / NIAID NIH HHS / United States
R01 HL095791 / HL / NHLBI NIH HHS / United States
F32 CA180653 / CA / NCI NIH HHS / United States
R01 HL134539 / HL / NHLBI NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States
R01 AI138546 / AI / NIAID NIH HHS / United States
U24 AI118672 / AI / NIAID NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
R01 CA219943 / CA / NCI NIH HHS / United States
K99 CA201592 / CA / NCI NIH HHS / United States
U54 CA217377 / CA / NCI NIH HHS / United States
R01 CA188228 / CA / NCI NIH HHS / United States
U19 AI089992 / AI / NIAID NIH HHS / United States
R01 DA046277 / DA / NIDA NIH HHS / United States