13 juin 2017

Comprendre les troubles du développement neurologique à l'aide de neurones humains dérivés de cellules souches pluripotentes

Aperçu: G.M.
La recherche sur les troubles psychiatriques a longtemps été entravée par l'absence de modèles appropriés. Les cellules souches pluripotentes induites (iPSC) offrent une source illimitée de cellules spécifiques au patient, qui en principe peuvent être différenciées dans tous les types de cellules somatiques pertinentes pour la maladie afin de créer des modèles in vitro du trouble visé.
Ici, les protocoles de différenciation neuronale disponibles à cette fin et les progrès actuels sur les modèles de schizophrénie, les "troubles du spectre de l'autisme" et le trouble bipolaire basés sur l'iPSC ont été examinés. 

Brain Pathol. 2017 Jul;27(4):508-517. doi: 10.1111/bpa.12517.

Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons

Author information

1
Neuroscience and Mental Health Research Institute, School of Medicine and School of Biosciences, Cardiff University, Cardiff, United Kingdom.

Abstract

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference "control" hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.
PMID:28585386
DOI:10.1111/bpa.12517

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