TCF12 controls oligodendroglial cell proliferation and regulates signaling pathways conserved in gliomas
| Autor: | Spehner, Daniele, Steyer, Anna, Bertinetti, Luca, Orlov, Igor, Benoit, Lucas, Pernet-Gallay, Karin, Schertel, Andreas, Schultz, Patrick |
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| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), schultz, patrick |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
proliferation
mouse model [SDV]Life Sciences [q-bio] Population Biology Transcriptome 03 medical and health sciences transcriptomics 0302 clinical medicine Glioma glioma medicine education Transcription factor 030304 developmental biology 0303 health sciences education.field_of_study Oligodendrocyte differentiation chromatin 60 immunoprecipitation medicine.disease Oligodendrocyte 3. Good health Chromatin Cell biology [SDV] Life Sciences [q-bio] medicine.anatomical_structure TCF12/HEB Signal transduction 030217 neurology & neurosurgery oligodendrocyte |
| Zdroj: | Journal of Structural Biology |
| ISSN: | 1047-8477 1095-8657 |
| Popis: | Diffuse gliomas are primary brain tumors originating from the transformation of glial cells. In particular, oligodendrocyte precursor cells constitute the major tumor-amplifying population in the gliomagenic process. We previously identified the TCF12 gene, encoding a transcription factor of the E protein family, as being recurrently mutated in oligodendrogliomas. In this study, we sought to understand the function of TCF12 in oligodendroglial cells, the glioma lineage of origin. We first describe TCF12 mRNA and protein expression pattern in oligodendroglial development in the mouse brain. Second, by TCF12 genome wide chromatin profiling in oligodendroglial cells, we show that TCF12 binds active promoters of genes involved in proliferation, translation/ribosomes, and pathways involved in oligodendrocyte development and cancer. Finally, we perform OPC-specific Tcf12 inactivation in vivo and demonstrate by immunofluorescence and transcriptomic analyses that TCF12 is transiently required for OPC proliferation but dispensable for oligodendrocyte differentiation. We further show that Tcf12 inactivation results in deregulation of biological processes that are also altered in oligodendrogliomas. Together, our data suggest that TCF12 directly regulates transcriptional programs in oligodendroglia development that are relevant in a glioma context. |
| Databáze: | OpenAIRE |
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