期刊
SCIENCE
卷 355, 期 6332, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aai8478
关键词
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资金
- Smith Family Foundation
- V Foundation for Cancer Research
- Merkin Institute Fellows at the Bead Institute
- American Cancer Society
- NIH-NCI brain cancer SPORE [P50CA165962]
- Broad Institute Broadnext10 program
- National Brain Turner Society
- Rachel Molly Markoff Foundation
- NIH [NS065743]
- American Brain. Tumor Association and Neurosurgery Research and Education Foundation
- Human Frontier Science Program fellowship
- Rothschild fellowship
- Placide Nicod Foundation
- EMBO long-term fellowship
- Burroughs-Wellcome Fund CAMS
- K12 Paul Calabresi Career Award for Clinical Oncology Training Program in Nervous System Tumors [K12CA090354]
- Hughes Medical Institute
- Klarman Family Foundation
- STARR cancer consortium
- NCI [1U24CA180922, R33CA202820]
- Koch Institute Support from NCI [P30-CA14051]
- Ludwig Center
- Me Broad Institute
- Burroughs-Wellcome Fund CAMS [BPIF 1007616.02]
- California Institute of Regenerative Medicine [RB4-06093, RN3-06510]
- Virginia and D. K. Ludwig Fund for Cancer Research
- MGH Department of Pathology
- [1S10RR023440-01A1]
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation. As tumor grade increases, we find enhanced proliferation of malignant cells, larger pools of undifferentiated glioma cells, and an increase in macrophage over microglia expression programs in TME. Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissecting the differences among human tumor subclasses.
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