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Table of contents
Absracts
Acknowledgements
Résumé extensif en français
Table of contents
Table of Figures
List of Acronyms
Introduction
Part I: Development of Oligodendroglial cells
1. Stem cells in the neocortex: the origins of neurons and glia
2. Defining “oligodendrocytes” (OLs) and “oligodendrogenesis”
3. Defining “oligodendrocyte precursor cells” (OPCs)
3.1 Embryonic origin of OPCs
3.2 OPCs in the postnatal and adult brain
3.3 Differentiation of OPCs to OLs
3.4 Heterogeneity of OPCs and OLs
4. Regulation of oligodendrogenesis
4.1 Transcriptional regulation
4.2 Regulation by developmental signaling pathways
4.3 Epigenetic regulation
Part II: Gliomas
1. Defining “gliomas”
2. Glioma epidemiology and classification
2.1 Epidemiological data and standard of care
2.2 Glioma classification by the World Health Organization (WHO)
3. Molecular alterations in adult diffuse gliomas
3.1 IDH-mutant gliomas (astrocytomas and oligodendrogliomas)
3.1.a IDH mutations
3.1.b Other common molecular alterations in IDH-mutant gliomas
3.2 IDH-wild type gliomas (GBM)
4. Defining “Glioma cells-of-origin” and “Glioma Stem Cells” (GSCs)
4.1 “Glioma-cells-of-origin” : putative candidates
4.1.a Neural stem cells as glioma cells-of-origin
4.1.b Oligodendrocyte precursors cells (OPCs) as glioma cells-of-origin
4.1.c Differentiated cells as glioma cells-of-origin
4.2 Glioma Stem Cells (GSCs): from subpopulations to functional states
4.2.a Early studies of GSCs
4.2.b GSCs in the era of single cell transcriptomics
5. Tumoral heterogeneity in gliomas
6. The glioma “ecosystem” and its microenvironment
Part III: TCF12 in the CNS and in gliomas
1. TCF12 is mutated in oligodendrogliomas
2. TCF12 belongs to the E protein class of the bHLH family
3. TCF12 roles in development
4. TCF12 roles in the CNS
5. TCF12 roles in cancer
Objectives
Results
Part I: Submitted manuscript
Extensive summary
Submitted manuscript
Introduction
Methods
Results
Figure 1: TCF12 is altered in gliomas.
Supplementary Figure 1 (related to Figure 1)
Figure 2: TCF12 is expressed in oligodendroglial cells
Supplementary Figure 2 (related to Figure 2)
Figure 3: TCF12 mainly occupies active promoter regions in oligodendroglial cells.
Supplementary Figure 3 (related to Figure 3)
Figure 4: TCF12 inactivation in OPCs in vivo results in proliferation defects
Supplementary Figure 4 (related to Figure 4)
Figure 5: Transcriptomic analyses of Tcf12 inactivated cells highlight defects in OPC proliferation, differentiation, and cancer-related pathways, that are conserved in hum
Supplementary Figure 5 (related to Figure 5)
Discussion
References
Part II: Additional results
Tcf12 inactivation in a glioma mouse model
Introduction
Results
Survival analysis
Histological analysis
[17]
Transcriptomic analyses
RT-qPCR
Bulk RNA-Sequencing
Methods
Discussion
Overview
1. TCF12 expression in oligodendroglial cells
2. Identification of TCF12 targets in oligodendroglial cells
3. Consequences of Tcf12 inactivation in OPCs in vivo
3.a. Histological analyses of Tcf12 knock-out mice
3.b.Transcriptomic analyses of Tcf12-deficient oligodendroglial cells
4. Parallels between TCF12 roles in oligodendrogenesis and gliomagenesis .
Outlook
Appendices
Appendix 1
Appendix 2
Appendix 3
Appendix 4
Appendix 5
Appendix 6
Appendix 7
Appendix 8
Appendix 9
Appendix 10
Appendix 11
Appendix 12
Bibliography
