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The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetic...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564557/ https://www.ncbi.nlm.nih.gov/pubmed/28525381 http://dx.doi.org/10.18632/oncotarget.17589 |
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author | Solga, Anne C Toonen, Joseph A Pan, Yuan Cimino, Patrick J Ma, Yu Castillon, Guillaume A Gianino, Scott M Ellisman, Mark H Lee, Da Yong Gutmann, David H |
author_facet | Solga, Anne C Toonen, Joseph A Pan, Yuan Cimino, Patrick J Ma, Yu Castillon, Guillaume A Gianino, Scott M Ellisman, Mark H Lee, Da Yong Gutmann, David H |
author_sort | Solga, Anne C |
collection | PubMed |
description | Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2(+) cells and that Olig2(+) oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2(+) OPCs could be tumor-initiating cells for Nf1 optic glioma. Similar to the GFAP-Cre transgenic strain previously employed to generate Nf1 optic gliomas, Olig2(+) cells also give rise to astrocytes in the murine optic nerve in vivo. However, in contrast to the GFAP-Cre strain where somatic Nf1 inactivation in embryonic neural progenitor/stem cells (Nf1(flox/mut); GFAP-Cre mice) results in optic gliomas by 3 months of age in vivo, mice with Nf1 gene inactivation in Olig2(+) OPCs (Nf1(flox/mut); Olig2-Cre mice) do not form optic gliomas until 6 months of age. These distinct patterns of glioma latency do not reflect differences in the timing or brain location of somatic Nf1 loss. Instead, they most likely reflect the cell of origin, as somatic Nf1 loss in CD133(+) neural progenitor/stem cells during late embryogenesis results in optic gliomas at 3 months of age. Collectively, these data demonstrate that the cell of origin dictates the time to tumorigenesis in murine optic glioma. |
format | Online Article Text |
id | pubmed-5564557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55645572017-08-23 The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation Solga, Anne C Toonen, Joseph A Pan, Yuan Cimino, Patrick J Ma, Yu Castillon, Guillaume A Gianino, Scott M Ellisman, Mark H Lee, Da Yong Gutmann, David H Oncotarget Research Paper Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2(+) cells and that Olig2(+) oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2(+) OPCs could be tumor-initiating cells for Nf1 optic glioma. Similar to the GFAP-Cre transgenic strain previously employed to generate Nf1 optic gliomas, Olig2(+) cells also give rise to astrocytes in the murine optic nerve in vivo. However, in contrast to the GFAP-Cre strain where somatic Nf1 inactivation in embryonic neural progenitor/stem cells (Nf1(flox/mut); GFAP-Cre mice) results in optic gliomas by 3 months of age in vivo, mice with Nf1 gene inactivation in Olig2(+) OPCs (Nf1(flox/mut); Olig2-Cre mice) do not form optic gliomas until 6 months of age. These distinct patterns of glioma latency do not reflect differences in the timing or brain location of somatic Nf1 loss. Instead, they most likely reflect the cell of origin, as somatic Nf1 loss in CD133(+) neural progenitor/stem cells during late embryogenesis results in optic gliomas at 3 months of age. Collectively, these data demonstrate that the cell of origin dictates the time to tumorigenesis in murine optic glioma. Impact Journals LLC 2017-05-03 /pmc/articles/PMC5564557/ /pubmed/28525381 http://dx.doi.org/10.18632/oncotarget.17589 Text en Copyright: © 2017 Solga et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Solga, Anne C Toonen, Joseph A Pan, Yuan Cimino, Patrick J Ma, Yu Castillon, Guillaume A Gianino, Scott M Ellisman, Mark H Lee, Da Yong Gutmann, David H The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title | The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title_full | The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title_fullStr | The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title_full_unstemmed | The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title_short | The cell of origin dictates the temporal course of neurofibromatosis-1 (Nf1) low-grade glioma formation |
title_sort | cell of origin dictates the temporal course of neurofibromatosis-1 (nf1) low-grade glioma formation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564557/ https://www.ncbi.nlm.nih.gov/pubmed/28525381 http://dx.doi.org/10.18632/oncotarget.17589 |
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