BookEmanuel DiCicco-Bloom, James H. Millonig, editors.
Summary: This book contains a compendium of induced pluripotent stem cells (iPSCs) articles and reviews concerning state of the art technologies and how they are being applied to human neurodevelopmental disorders. With the establishment of effective technologies to produce iPSCs and their derivatives, like neural precursors, neurons, and glia, researchers have new platforms to study neurodevelopmental disorders. iPSC technology enables researchers to study how human neurons develop in individuals with neurodevelopmental disorders, providing an unparalleled opportunity to investigate their etiology. In turn, researchers have now begun to understand the underlying molecular and cellular pathways that contribute to human diseases. iPSCs technologies also provide an emerging tool for future translational studies and disease classification. The chapters will emphasize how among the diverse idiopathic and genetic disorders, there are common clinical as well as cellular and molecular phenotypes.
Contents:
Intro
Contents
About the Editors
Modeling Neurodevelopmental Deficits in Tuberous Sclerosis Complex with Stem Cell Derived Neural Precursors and Neurons
1 Background of Tuberous Sclerosis Complex
1.1 Neurology of TSC
1.2 mTORC1 and mTORC2
2 Neural Stem Cell Development in TSC
2.1 TSC2 Deficiency in hESCs and hiPSCs
2.2 Effects of mTORC1 Pathway Activation in Human Neural Stem Cell Proliferation
2.3 Differentiation Capacity and Morphological Development of TSC-Deficient Stem Cell Derived NPCs
2.4 Abnormal Purkinje Cell Differentiation of TSC2-Deficient hiPSCs 3 Gliosis and Myelination in TSC
3.1 Astrocyte Differentiation from TSC-Deficient Neural Precursor Cells
3.2 Development of Oligodendrocytes and Myelination Deficits in TSC
4 Cellular Homeostasis and Viability in TSC
4.1 Mitochondrial Dysfunction in TSC
4.2 Autophagy in TSC
5 Autism and Epilepsy in TSC
5.1 MTOR-Pathway in Autism and Epilepsy
5.2 Tsc-Deficient Rodent Models of Epilepsy and Autism
5.3 Genes Associated with Neural Differentiation and Synaptic Development in TSC2-Deficient Human Neurons 3.1 Unique Features of Human Genetics and Neural Development Require Human FXS Models
3.2 Human Pluripotent Stem Cells as a Platform to Understand the Pathogenesis of FXS
3.3 Human PSCs for Understanding FMR1 Silencing in FXS
4 Human PSCS for Targeting FMR1 Gene Reactivation for Treating FXS
4.1 Rationale for FMR1 Gene Restoration as a Potential Therapy
4.2 FMR1 Gene Restoration Strategies by Targeting Known Pathways
4.3 Search for Novel FMR1 Gene Restoration Strategies Using High-Throughput Screening of Chemicals
4.4 FMR1 Gene Reactivation by Genetic Targeting of CGG Repeats 5 Summary: Challenges and Perspectives
References
IPSC Models of Chromosome 15Q Imprinting Disorders: From Disease Modeling to Therapeutic Strategies
1 Prader-Willi Syndrome
2 Angelman Syndrome
3 15q11-q13 Duplication
4 Special Considerations for Disease Models of Imprinting Disorders
5 Physiological and Morphological Phenotypes
5.1 Cellular Phenotypes in Angelman Syndrome-Derived Neurons
5.2 Cellular Phenotypes in Dup15q Syndrome-Derived Neurons
5.3 Cellular Phenotypes in Prader-Willi Syndrome-Derived Neurons 5.4 Synaptic Function and Excitability of TSC2-Deficient Human Neurons
6 Future Prospects
6.1 Pharmacological Treatment of Neurological Deficits in TSC
6.2 Drug Screening Assays in TSC2-Deficient Human Neurons
References
Advances in Human Stem Cells and Genome Editing to Understand and Develop Treatment for Fragile X Syndrome
1 Introduction
2 Unique and Complex Genetics of FXS
2.1 CGG Expansion of the Human FMR1 Gene
2.2 Epigenetic Silencing of the Human FMR1 Gene
3 Human Pluripotent Stem Cells Models for FXS