Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells

被引:28
作者
Watmuff, Bradley [1 ,2 ,3 ,4 ]
Berkovitch, Shaunna S. [1 ,2 ,4 ]
Huang, Joanne H. [1 ,2 ,4 ]
Iaconelli, Jonathan [1 ,2 ,4 ]
Toffel, Steven [1 ,2 ,3 ,4 ]
Karmacharya, Rakesh [1 ,2 ,3 ,4 ,5 ]
机构
[1] Harvard Univ, Sch Med, Ctr Expt Drugs & Diagnost, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA
[3] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA
[4] Broad Inst Harvard & MIT, Ctr Sci Therapeut, Cambridge, MA 02142 USA
[5] McLean Hosp, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02478 USA
关键词
Schizophrenia; Bipolar disorder; Stem cells; IPSC; Microglia; Gene-environment; Neuronal differentiation; COMORBIDITY SURVEY REPLICATION; CORTICAL PYRAMIDAL NEURONS; DENDRITIC SPINE DENSITY; TERM LITHIUM TREATMENT; HUMAN CEREBRAL-CORTEX; HUMAN FIBROBLASTS; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; BRAIN-DEVELOPMENT; NATURAL-HISTORY;
D O I
10.1016/j.mcn.2016.01.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:96 / 103
页数:8
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