Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, 01595, USA.
Department of Pathology, New York Medical College, Valhalla, NY, 01595, USA.
J Psychiatr Res. 2021 May;137:111-116. doi: 10.1016/j.jpsychires.2021.02.054. Epub 2021 Feb 27.
Cortical interneurons (cINs) are substantially affected in Schizophrenia (SCZ) and enriched for SCZ heritability during development. To understand SCZ-specific changes in these cells during development, we isolated migratory cINs from cIN spheres derived from 5 healthy control (HC) and 5 SCZ induced pluripotent stem cell lines (iPSCs). Transcriptome analyses show dysregulation in extracellular matrix pathways as the major disturbances in SCZ migratory cINs, whereas sphere cINs show dysregulation in immune pathways. This result suggests the importance of using homogeneous cell populations to identify stage-specific abnormalities and provides a platform to further study the biology of schizophrenia pathogenesis during early development.
皮质中间神经元（cINs）在精神分裂症（SCZ）中受到显著影响，并且在发育过程中富集了 SCZ 的遗传率。为了在发育过程中理解这些细胞中与 SCZ 特异性相关的变化，我们从源自 5 名健康对照（HC）和 5 名 SCZ 诱导多能干细胞系（iPSC）的 cIN 球体中分离出迁移中的 cIN。转录组分析表明，细胞外基质途径的失调是 SCZ 迁移 cIN 的主要干扰因素，而球体 cIN 则表现出免疫途径的失调。这一结果表明，使用同质细胞群体来识别特定阶段的异常是很重要的，并为进一步研究早期发育过程中精神分裂症发病机制的生物学提供了一个平台。
