Impaired migration of autologous induced neural stem cells from patients with schizophrenia and implications for genetic risk for psychosis

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Lee, Junhee; Song, Sehyeon; Lee, Juhee; Kang, Jisoo; Choe, Eun Kyung; Lee, Tae Young; Chon, Myong-Wuk; Kim, Minah; Kim, Seong Who; Chun, Myung-Suk; Chang, Mi-Sook; Kwon, Jun Soo

Issue Date
Elsevier BV
Schizophrenia Research, Vol.246, pp.225-234
Stem cell technologies have presented explicit evidence of the neurodevelopmental hypothesis of schizophrenia. However, few studies investigated relevance of the schizophrenia genetic liability and the use of genetic reprogramming on pluripotent stem cells to the impaired neurodevelopment shown by stem cells. Therefore, this study sought to investigate the cellular phenotypes of induced neural stem cells (iNSCs) derived without genetic modification from patients with schizophrenia and from genetic high risk (GHR) individuals. Three patients with a diagnosis of schizophrenia, 3 GHR individuals who had two or more relatives with schizophrenia, and 3 healthy volunteers participated. iNSCs were derived using a small molecule-based lineage switch method, and their gene expression levels and migration capabilities were examined. Demographic characteristics were not different among the groups (age, chi(2) = 5.637, P = .060; education, chi(2) = 2.111, P = .348). All participants stayed well during the follow-up except one GHR individual who developed psychosis 1.5 years later. Migration capacity was impaired in iNSCs from patients with schizophrenia (SZ-iNSCs) compared to iNSCs from GHR individuals or controls (P < .001). iNSCs from a GHR individual who later developed schizophrenia showed migratory impairment that was similar to SZ-iNSCs. Gene expression levels of Sox2 in SZ-iNSCs were significantly lower than those in controls (P = .028). Defective migration in genetically unmodified SZ-iNSCs is the first direct demonstration of neurodevelopmental abnormalities in schizophrenia. Additionally, alterations in gene expression in SZ-iNSCs suggest mechanisms by which genetic liability leads to aberrant neurodevelopment.
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College of Natural Sciences (자연과학대학)Brain and Cognitive Sciences (뇌인지과학과)Journal Papers (저널논문_뇌인지과학과)
College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dental Science(치의과학과)Journal Papers (저널논문_치의과학과)
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