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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 <jats:italic>DGCR8<\/jats:italic>, a key gene for microRNA (miRNA) processing and mapped in the deleted region. In mice, <jats:italic>Dgcr8<\/jats:italic> hetero-knockout is known to show a similar phenotype of reduced neurosphere size (Ouchi <jats:italic>et al.<\/jats:italic>, 2013). The miRNA profiling detected reduced expression levels of miRNAs belonging to miR-17\/92 cluster and miR-106a\/b in the patient-derived neurospheres. Those miRNAs are reported to target p38\u03b1, and conformingly the levels of p38\u03b1 were upregulated in the patient-derived cells. p38\u03b1 is known to drive gliogenic differentiation. The inhibition of p38 activity by SB203580 in patient-derived neurospheres partially restored neurogenic competence. Furthermore, we detected elevated expression of <jats:italic>GFAP<\/jats:italic>, a gliogenic (astrocyte) marker, in postmortem brains from schizophrenia patients without the 22q11.2 deletion, whereas inflammation markers (<jats:italic>IL1B<\/jats:italic> and <jats:italic>IL6<\/jats:italic>) remained unchanged. In contrast, a neuronal marker, <jats:italic>MAP2<\/jats:italic> expressions were decreased in schizophrenia brains. These results suggest that a dysregulated balance of neurogenic-to-gliogenic competence may underlie neurodevelopmental disorders such as schizophrenia.<\/jats:p>","DOI":"10.1038\/tp.2016.206","type":"journal-article","created":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T14:43:48Z","timestamp":1478011428000},"page":"e934-e934","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Analysis of induced pluripotent stem cells carrying 22q11.2 deletion"],"prefix":"10.1038","volume":"6","author":[{"given":"M","family":"Toyoshima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Akamatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Ohnishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Balan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Hisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Iwayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Toyota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Itasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Okano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,1]]},"reference":[{"key":"BFtp2016206_CR1","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.tig.2009.10.006","volume":"25","author":"AK Merikangas","year":"2009","unstructured":"Merikangas AK, Corvin AP, Gallagher L . 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