Journal article
Analysis of induced pluripotent stem cells carrying 22q11.2 deletion
M Toyoshima, W Akamatsu, Y Okada, T Ohnishi, S Balan, Y Hisano, Y Iwayama, T Toyota, T Matsumoto, N Itasaka, S Sugiyama, M Tanaka, M Yano, B Dean, H Okano, T Yoshikawa
Translational Psychiatry | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/tp.2016.206
Abstract
Given the complexity and heterogeneity of the genomic architecture underlying schizophrenia, molecular analyses of these patients with defined and large effect-size genomic defects could provide valuable clues. We established human-induced pluripotent stem cells from two schizophrenia patients with the 22q11.2 deletion (two cell lines from each subject, total of four cell lines) and three controls (total of four cell lines). Neurosphere size, neural differentiation efficiency, neurite outgrowth, cellular migration and the neurogenic-to-gliogenic competence ratio were significantly reduced in patient-derived cells. As an underlying mechanism, we focused on the role of DGCR8, a key gene for mi..
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Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank the late Motoichiro Kato of the Department of Psychiatry, Keio University School of Medicine, for the recruitment of a patient. We also thank members of Okano's laboratory for support of iPSCs establishment and culture. We are grateful to the Support Unit for Bio-Material Analysis at RIKEN BSI Research Resource Center, for technical help with array analysis. This study was supported in part by the Grant-in-Aid for Scientific Research (25861037, 15K09849 to MT) from Japan Society for the Promotion of Science and the Grant-in-Aid for Scientific Research on Innovative Areas (Unraveling the microendophenotypes of psychiatric disorders at the molecular, cellular and circuit levels; TY), the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and development, AMED (TY), AMED-CREST from Japan Agency for Medical Research and Development, AMED (TY) and Leading Project for Realization of Regenerative Medicine (HO) from the Ministry of Education, Culture, Sports, Science and Technology. In addition, this study was supported by 'Funding Program for World-Leading Innovative R&D on Science and Technology' (HO) and RIKEN Brain Science Institute Fund (TY) and NHMRC Fellowship (APP1002240 to BD).