Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
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, the...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125052 |
| _version_ | 1826201181374906368 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:47:48Z |
| format | Article |
| id | mit-1721.1/125052 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:47:48Z |
| publishDate | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1250522022-09-27T21:57:34Z Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq Regev, Aviv Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. National Cancer Institute (U.S.) (Grant 1U24CA180922) National Cancer Institute (U.S.) (Grant R33CA202820) National Cancer Institute (U.S.) (Grant P30-CA14051) 2020-05-06T15:28:49Z 2020-05-06T15:28:49Z 2018-04 2020-01-28T17:13:04Z Article http://purl.org/eprint/type/JournalArticle 0193-4511 https://hdl.handle.net/1721.1/125052 Filbin, Mariella G. et al. “Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.” Science 360 (2018): 331-335 © 2018 The Author(s) en 10.1126/SCIENCE.AAO4750 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Regev, Aviv Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title | Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title_full | Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title_fullStr | Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title_full_unstemmed | Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title_short | Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq |
| title_sort | developmental and oncogenic programs in h3k27m gliomas dissected by single cell rna seq |
| url | https://hdl.handle.net/1721.1/125052 |
| work_keys_str_mv | AT regevaviv developmentalandoncogenicprogramsinh3k27mgliomasdissectedbysinglecellrnaseq |