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Table of contents
1. Regional Heterogeneity and Competence of Neural Stem Cells Throughout Development and Postnatal Life
1.1. The Developing Forebrain Generates Neuronal Diversity
1.1.1 Diversity of the Progenitors during Cortical Neurogenesis
1.1.2 Regionalization of the Developing Brain
1.1.3. Basic Principles of Cortical Organization
1.1.4. Molecular Diversity of Anatomically Defined PNs
1.2. Germinal Activity Persists in the Postnatal SVZ
1.2.1. The Postnatal Niche
1.2.2. The Radial Glia Origin of Type B1 Cells:
1.2.3. Type B1 Cells: A Specialized Astrocyte
1.2.4. Regionalization and heterogeneity of Postnatal SVZ NSCs
1.2.5. Regionalization also applied to gliogenesis
1.2.6. Signals from the CSF and the niche act in concert to regulate NSCs activity and regionalization throughout pre- and postnatal life
1.3. Transcriptional correlates of SVZ NSCs regionalization
1.4. Objectives of the PhD thesis
2. Experimental Chapter 1: HOPX Defines Heterogeneity of Postnatal Subventricular Zone Neural Stem Cells
2.1. Introduction
2.2. Experimental procedures
2.3. Results
Hopx Is Enriched in NSCs of the dSVZ and in Cells of the Astrocytic Lineage.
HOPX Expression Reveals Intraregional Heterogeneity within the dSVZ
The dSVZ Is Defined by Microdomains with Distinct Lineage Outputs
HOPX-Expressing dNSCs Are Biased to Acquire an Astroglial Fate
Hopx-expressing RGCs are Present in the Late Developing pallium and Share Transcriptional Featrues with adult Astrocytes
2.4. Discussion
2.5. Supplementary Figures
3. Experimental Chapter 2: Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period
3.1. Introduction
3.2. Experimental Procedures
3.3. Results
Fate Mapping of Birth-Dated Cohorts of Glutamatergic Neurons
A Large Population of Glu Progenitors Persist in the Postnatal SVZ
ScRNA-Seq Reveals Transcriptional Dysregulation in Postnatal Glu Progenitors
Postnatal Glu Progenitor Differentiation Can Be Partially Rescued
3.4. Discussion
3.4. Supplementary Figures
4. General Discussion
4.1. Summary and Opened Questions
4.2. Contributions of Single cell Approaches to Probe Neural Progenitor’s Heterogeneity and Dynamics
4.2.1. Clonal Techniques in Histology and Transcriptomic
4.2.2. Contributions of Single Cell Approaches to Probe Spatial Identity Specification
4.2.3. Contributions of Single cell Approaches to Probe Temporal Identity Specification
4.2.4. Contributions of Single cell Approaches to Probe Adult NSCs Origin and Biology
4.3. Implication for Brain Repair
4.3.1 Are embryonic and Postnatal/adult NSCs Representing Distinct Populations in term of Diversity and Competence?
4.3.2. Targeted Neuronal Ablation as a Model to Study Competence of Postnatal NSCs for Cortical Repair
5. Annexes
6. References
7. CV
8. List of Publications
9. Additional Publications
