TitleSelf-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection.
Publication TypeJournal Article
Year of Publication2017
AuthorsWatanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, Coppola G, Pearson CA, Yamauchi K, Gong D, Dai X, Damoiseaux R, Aliyari R, Liebscher S, Schenke-Layland K, Caneda C, Huang EJ, Zhang Y, Cheng G, Geschwind DH, Golshani P, Sun R, Novitch BG
JournalCell Rep
Volume21
Issue2
Pagination517-532
Date Published2017 Oct 10
ISSN2211-1247
KeywordsAnti-Retroviral Agents, c-Mer Tyrosine Kinase, Cell Line, Cerebral Cortex, Drug Evaluation, Preclinical, Embryonic Stem Cells, Humans, Neurons, Organoids, Primary Cell Culture, Receptor Protein-Tyrosine Kinases, STAT3 Transcription Factor, Zika Virus
Abstract

The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we describe optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of this organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions.

DOI10.1016/j.celrep.2017.09.047
Alternate JournalCell Rep
PubMed ID29020636
PubMed Central IDPMC5637483
Grant ListR01 MH094714 / MH / NIMH NIH HHS / United States
P01 NS083513 / NS / NINDS NIH HHS / United States
U54 HD087101 / HD / NICHD NIH HHS / United States
R01 MH100027 / MH / NIMH NIH HHS / United States
R01 MH110927 / MH / NIMH NIH HHS / United States
R01 AI069120 / AI / NIAID NIH HHS / United States
R00 NS089780 / NS / NINDS NIH HHS / United States
P30 NS062691 / NS / NINDS NIH HHS / United States
R01 MH060233 / MH / NIMH NIH HHS / United States
U01 MH103339 / MH / NIMH NIH HHS / United States
R01 AI056154 / AI / NIAID NIH HHS / United States
R01 NS085227 / NS / NINDS NIH HHS / United States
R01 AI078389 / AI / NIAID NIH HHS / United States
R01 NS089817 / NS / NINDS NIH HHS / United States