RT Journal Article
SR Electronic
T1 In Vitro Modeling of the Bipolar Disorder and Schizophrenia Using Patient-Derived Induced Pluripotent Stem Cells with Copy Number Variations of PCDH15 and RELN
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0403-18.2019
DO 10.1523/ENEURO.0403-18.2019
VO 6
IS 5
A1 Ishii, Takaya
A1 Ishikawa, Mitsuru
A1 Fujimori, Koki
A1 Maeda, Takuji
A1 Kushima, Itaru
A1 Arioka, Yuko
A1 Mori, Daisuke
A1 Nakatake, Yuhki
A1 Yamagata, Bun
A1 Nio, Shintaro
A1 Kato, Takahiro A.
A1 Yang, Nan
A1 Wernig, Marius
A1 Kanba, Shigenobu
A1 Mimura, Masaru
A1 Ozaki, Norio
A1 Okano, Hideyuki
YR 2019
UL http://www.eneuro.org/content/6/5/ENEURO.0403-18.2019.abstract
AB Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patient with contributive copy number variations, as follows: two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2 (microtubule-associated protein 2)-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15- or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders.