Journal
SCIENCE
Volume 360, Issue 6386, Pages 331-335Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao4750
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Funding
- Alex Lemonade Stand
- Wang Family Fund
- Smith Family Foundation
- Broad Institute Broadnext10
- V Foundation for Cancer Research
- Howard Goodman Fellowship at Massachussetts General Hospital (MGH)
- Merkin Institute Fellowship at the Broad Institute of MIT and Harvard
- Rachel Molly Markoff Foundation
- NIH-National Cancer Institute (NCI) brain cancer SPORE [P50CA165962]
- MGH department of Pathology
- Cure Starts Now Foundation
- Hope for Caroline Foundation
- Julian Boivin Courage for Cures Foundation
- Abbie's Army
- Michael Mosier Defeat DIPG Foundation
- Reflections of Grace Foundation
- Cure Starts Now Australia
- Brooke Healey Foundation
- Soar With Grace Foundation
- Jeffrey Thomas Hayden Foundation
- Cure Brain Cancer Foundation
- Jones Family Foundation
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- Benny's World
- Love Chloe Foundation
- Aiden's Avengers
- A Cure from Caleb Society
- Operation Grace White Foundation
- Ryan's Hope
- Wayland Villars DIPG Foundation
- American Childhood Cancer Organization
- Juliana Rose Donnelly Trust
- Sheila Jones Friends
- Ellie Kavalieros DIPG Research Fund
- Voices Against Brain Cancer
- DIPG Collaborative
- Zach Carson Foundation
- Micky Czech Foundation
- Guglietti Family Trust
- Prayers From Maria Foundation
- Ryan Harvey Foundation
- Markoff Art in Giving
- Brock Fleming Foundation
- Burroughs Wellcome Fund
- K12 Paul Calabresi Career Award for Clinical Oncology-Training Program in Nervous System Tumors [K12CA090354]
- Zuckerman STEM Leadership Program
- Benoziyo Endowment Fund for the Advancement of Science
- European Molecular Biology Organization long-term fellowship
- Human Frontier Science Program fellowship
- Placide Nicod Foundation
- NCI [P01 CA142536, R01CA219943, R01CA188228, R33CA202820]
- Fondation Nuovo-Soldati
- St. Baldrick's Foundation
- Pediatric Brain Tumor Foundation
- Gray Matters Brain Cancer Foundation Olivia Caldwell Foundation
- Howard Hughes Medical Institute
- Klarman Cell Observatory
- STARR cancer consortium
- Koch Institute Support (core) grant from NCI [P30-CA14051]
- Ludwig Center
- Broad Institute
- NIH Common Fund
- National Cancer Institute [DP1CA216873]
- American Cancer Society
- Ludwig Center at Harvard Medical School
- Bernard and Mildred Kayden MGH Research Institute Chair
- California Institute of Regenerative Medicine (CIRM) [RB4-06093, RN3-06510]
- Lyla Nsouli Foundation
- Virginia and D. K. Ludwig Fund for Cancer Research
- Alicia Pueyo Foundation
- [1S10RR023440-01A1]
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Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.
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