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Free keywords:
GENOME-WIDE ASSOCIATION; NEURODEVELOPMENTAL DISORDERS;
CRITICAL-APPRAISAL; CLINICAL-OUTCOMES; GENETIC-LOCI; HUMAN IPSCS;
SCHIZOPHRENIA; DIFFERENTIATION; RISK; MICRORNASBiochemistry & Molecular Biology; Chemistry; bipolar disease; patient-specific iPSC; early neurodevelopment; lithium;
neuronal excitability; calcium signaling;
Abstract:
Bipolar disease (BD) is one of the major public health burdens worldwide and more people are affected every year. Comprehensive genetic studies have associated thousands of single nucleotide polymorphisms (SNPs) with BD risk; yet, very little is known about their functional roles. Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype in disease-relevant tissues and cell types. Neural cells generated from BD-specific iPSCs are thought to capture associated genetic risk factors, known and unknown, and to allow the analysis of their effects on cellular and molecular phenotypes. Interestingly, an increasing number of studies on BD-derived iPSCs report distinct alterations in neural patterning, postmitotic calcium signaling, and neuronal excitability. Importantly, these alterations are partly normalized by lithium, a first line treatment in BD. In light of these exciting findings, we discuss current challenges to the field of iPSC-based disease modelling and future steps to be taken in order to fully exploit the potential of this approach for the investigation of BD and the development of new therapies.
