AUTHOR=Iwasa Naoki , Matsui Takeshi K. , Iguchi Naohiko , Kinugawa Kaoru , Morikawa Naritaka , Sakaguchi Yoshihiko M. , Shiota Tomo , Kobashigawa Shinko , Nakanishi Mari , Matsubayashi Masaya , Nagata Riko , Kikuchi Sotaro , Tanaka Tatsuhide , Eura Nobuyuki , Kiriyama Takao , Izumi Tesseki , Saito Kozue , Kataoka Hiroshi , Saito Yuichi , Kimura Wataru , Wanaka Akio , Nishimura Yuhei , Mori Eiichiro , Sugie Kazuma TITLE=Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation JOURNAL=Frontiers in Cellular Neuroscience VOLUME=15 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.605030 DOI=10.3389/fncel.2021.605030 ISSN=1662-5102 ABSTRACT=

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.