Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 21 for “"Brain organoids"”.
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Characterising molecular and cellular mechanisms of human brain evolution using brain organoids
… of humans is marked by a rapid expansion in brain size. Efforts to study human brain evolution have characteristically relied on anatomical and genomic comparisons between adult ape brains, meaning that the molecular mechanisms underlying human-specific brain expansion remain largely unknown. …
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Human Brain Organoids for Studying Malignant Cell States and Intercellular Communication in Human Glioma
… of the disease. In recent years, human brain organoids have emerged as promising 3D, in vitro model systems for partially recreating the cellular composition and function of the human brain. In the context of this research, human brain organoids represent a potential construct through …
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BRAIN ORGANOIDS AS MODELLING CONDUITS OF HUMAN NEURODIVERSITY: ADVANCED COMPUTATIONAL APPROACHES TO SINGLE CELL TRANSCRIPTOMICS
… processes. The introduction of human brain organoids (BOs), allowed to reach an unprecedented experimental tractability of brain development trajectories, surpassing the limitations of their preceding 2D models and of animal models in recapitulating CNS cytoarchitecture. The advent of …
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THE INTERPLAY BETWEEN ENDOCRINE DISRUPTION AND GENETICS IN THE PHYSIOPATHOLOGY OF HUMAN NEURODEVELOPMENT: BRIDGING EPIDEMIOLOGY TO MOLECULAR INSIGHTS THROUGH BRAIN ORGANOIDS AND HIGH RESOLUTION OMIC MODELLING
… pluripotent stem cells (hiPSC)-derived cortical brain organoids (CBOs), a model that recapitulates salient species-specific features of human brain development in a 3D microenvironment characterized by stereospecific interconnections among different cell populations. After chronically exposing …
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Comparative studies of brain developmental timing and progression using 3D stem cell models
The human brain is three times larger than those of our closest evolutionary relatives such as chimpanzees and gorillas, yet the mechanisms by which this increase in size has been achieved, and also the implications of this on human brain function and capabilities, remain largely yet to be …
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MICROGLIA-SUFFICIENT BRAIN ORGANOID
Embryonic primitive macrophages colonize the brain where they differentiate into microglia. Microglia were shown to contribute to brain development in animal models but their roles in human brain development remain poorly understood due to the lack of tissue access. The generation of brain …
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Interaction between form and fate during human neural development
… during neural development. We relied on cerebral organoids as a tractable *in vitro* system where tissue shape can be manipulated following several complementary approaches and tissue identity assessed by transcriptomics. We first discovered key protocol variables that contribute to differences in …
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DISSECTING THE ROLE OF GOLGI TRAFFIC IN BRAIN DEVELOPMENT ACROSS HEALTH AND DISEASE: A LESSON FROM COG5-CDG STUDIES
… Disorders of Glycosylation (CDGs). Notably, brain development impairments, such as primary microcephaly, are described in most CDG patients. Despite the increased number of diagnosed patients, the cell biological mechanisms linking defective Golgi glycosylation and neurodevelopmental …
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AGGREGATION MECHANISMS OF TDP-43 PROTEIN IN RESPONSE TO STRESS IN AMYOTROPHIC LATERAL SCLEROSIS AND THERAPEUTIC APPROACHES
… pluripotent stem cells (iPSCs)-motor neurons and brain organoids. As a readout of TDP-43 functionality, we tested its subcellular localization and its splicing activity towards the target genes UNC13A and POLDIP3. We demonstrated that chronic oxidative stress in these cellular models induced …
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Characterizing 3D epigenomes in pathological conditions
… chart the developmental progression of trisomic brain organoids. This single-cell transcriptomic analysis uncovered impaired differentiation pathways in trisomic stem cells, leading to suboptimal development into neural progenitor cells and neurons. By employing chromatin conformation capture …
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EZH1 variants disrupt neurogenesis in hPSC-derived neuronal models and cause neurodevelopmental disorders
… of EZH1 in the developing and adult human brain and a causal role of EZH1 variants in the disease pathogenesis. To test this hypothesis, we generated neurodevelopmental models derived from EZH1 LOF and GOF human pluripotent stem cells (hPSC). Our monolayer neuronal differentiations showed …
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Investigating circuit and spatial heterogeneity of human brain tumors with patient-derived organoid models
… glioblastoma (GBM), are aggressive adult primary brain cancers with dismal prognosis. Both malignant cell heterogeneity and the influence of myriad cell types present in the tumor microenvironment, such as neurons, contribute to glioma progression. This dissertation represents a multi-pronged …
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Investigating the role of ZEB2 in the establishment of neuroepithelial architecture and axon tract formation
… factor ZEB2 as a putative regulator of brain size. In this work we show that in both human brain organoids and mouse embryos ZEB2 is expressed in telencephalic neuroepithelial cells (NECs) before the switch to radial glia (RGCs). By establishing a human embryonic stem cell (hESC) model …
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PRC2 GATEKEEPS THE BALANCE BETWEEN DIRECT AND INDIRECT NEUROGENESIS AND CONTROLS NEURONAL MIGRATION DURING HUMAN CORTICOGENESIS
… epigenomic analyses of patient-derived cortical brain organoids (CBOs) cultured for up to 250 days in vitro. Our multi-omic approach integrated bulk and single-cell RNA sequencing, EZH2 and H3K27me3 genomic distribution mapping, and DNA methylation profiling. These analyses revealed disruptions …
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Bioinformatic Approaches to Study Mitochondrial DNA Heteroplasmy
… the disease’s progression, we cultivated brain organoids from MELAS patients for either 100 or 200 days. Computational analysis of single cell RNA sequencing revealed the cellular mechanisms behind disease progression. We found evidence of calcium trafficking dysregu lation, which is …
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High-Throughput Mapping of The Biological Effects of Particle Therapy
… glioma stem cell spheroids and normal rat brain organoids.</p> <p>For protons, all model systems demonstrated a rapid rise in RBE beyond the Bragg peak. These findings contrast with several current model predictions which assume the RBE trend linearly scales with proton LET. For the heavier …
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Multimethodological approaches to tackle glycogen: therapeutic and modelling opportunities in Lafora disease
… manner. PTG emerged as a master regulator of brain glycogen synthesis. In LD, PTG escapes degradation due to the dysfunctional laforin-malin complex, leading to the accumulation of PGBs and neurodegeneration. Presently, the landscape for LD remains barren of efficacious treatments, cellular …
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DEVELOPMENT OF NEW OLIGODENDROCYTE-BASED MODELS TO IDENTIFY PHARMACOLOGICAL AGENTS WITH REMYELINATING ACTIVITY
… white matter of human MS post-mortem brains, suggesting a potential role of GPR17-positive cells in inflammation. In the first part of the present thesis, we aimed at establishing an inflammatory model of OL differentiation impairment that is representative of MS and targeting GPR17 in …
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THE EVOLUTION OF THE MODERN CONDITION THROUGH THE LENS OF NEURODEVELOPMENT DIVERSITY: INSIGHTS FROM A PARADIGMATIC REWIRING OF GENE REGULATION
… reconfigured during the evolution of the Sapiens brain. Understanding how regulatory changes reconfigured the neurodevelopmental trajectories that underpin hallmark features of our species’ unique cognitive abilities requires the integration of computational and experimental approaches, pairing …
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