Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models.

Autor:	Haase FD; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Kids Neuroscience Centre, Kids Research, Children's Hospital at Westmead, Westmead, NSW, Australia.; Molecular Neurobiology Research Laboratory, Kids Research, Children's Hospital at Westmead, and Children's Medical Research Institute, Westmead, NSW, Australia., Coorey B; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Kids Neuroscience Centre, Kids Research, Children's Hospital at Westmead, Westmead, NSW, Australia.; Molecular Neurobiology Research Laboratory, Kids Research, Children's Hospital at Westmead, and Children's Medical Research Institute, Westmead, NSW, Australia., Riley L; Rare Diseases Functional Genomics Laboratory, Kids Research, Children's Hospital at Westmead, and Children's Medical Research Institute, Westmead, NSW, Australia., Cantrill LC; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Kids Research, Children's Hospital at Westmead, Westmead, NSW, Australia., Tam PPL; Embryology Research Unit, Children's Medical Research Institute, The University of Sydney, Sydney, NSW, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Gold WA; Kids Neuroscience Centre, Kids Research, Children's Hospital at Westmead, Westmead, NSW, Australia.; Molecular Neurobiology Research Laboratory, Kids Research, Children's Hospital at Westmead, and Children's Medical Research Institute, Westmead, NSW, Australia.; Rare Diseases Functional Genomics Laboratory, Kids Research, Children's Hospital at Westmead, and Children's Medical Research Institute, Westmead, NSW, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2021 Aug 25; Vol. 15, pp. 698812. Date of Electronic Publication: 2021 Aug 25 (Print Publication: 2021).
DOI:	10.3389/fnins.2021.698812
Abstrakt:	Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in MECP2 . The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets. Brain organoid models that recapitulate much of the tissue architecture and the complexity of cell types in the developing brain, offer further unprecedented opportunity for elucidating human neural development, without resorting to conventional animal models and the limited resource of human neural tissues. This review focuses on the new knowledge of RTT that has been gleaned from the iPSC-based models as well as limitations of the models and strategies to refine organoid technology in the quest for clinically relevant disease models for RTT and the broader spectrum of neurodevelopmental disorders. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Haase, Coorey, Riley, Cantrill, Tam and Gold.)
Databáze:	MEDLINE
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