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 2024-01-19T11:32:07Z 2024-01-19T11:32:07Z 2022-08-04 2022-08 0920-9964 https://pubs.kist.re.kr/handle/201004/114820 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. English Elsevier BV Impaired migration of autologous induced neural stem cells from patients with schizophrenia and implications for genetic risk for psychosis Article 10.1016/j.schres.2022.06.027 1 Schizophrenia Research, v.246, pp.225 - 234 Schizophrenia Research 246 225 234 N scie ssci scopus 000829292500005 Psychiatry Psychiatry Article ENTORHINAL CORTEX NEURONAL MIGRATION WHITE-MATTER FOLLOW-UP BRAIN ABNORMALITIES CYTOARCHITECTURE DISTURBANCES CONNECTIVITY DISORDERS Genetic high risk Neurodevelopment Neuronal migration Schizophrenia Stem cell