Journal
LIFE SCIENCE ALLIANCE
Volume 3, Issue 5, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202000707
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Funding
- Canada First Research Excellence Fund/Medicine by Design, Krembil Foundation
- Canadian Institute for Health Research (CIHR) Foundation [FDN148455, FDN143252]
- CIHR [PJT-148568]
- Canada Research Chair in Molecular Psychiatry grants
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Human cerebral organoid (hCO) models offer the opportunity to understand fundamental processes underlying human-specific cortical development and pathophysiology in an experimentally tractable system. Although diverse methods to generate brain organoids have been developed, a major challenge has been the production of organoids with reproducible cell type heterogeneity and macroscopic morphology. Here, we have directly addressed this problem by establishing a robust production pipeline to generate morphologically consistent hCOs and achieve a success rate of >80%. These hCOs include both a radial glial stem cell compartment and electrophysiologically competent mature neurons. Moreover, we show using immunofluorescence microscopy and single-cell profiling that individual organoids display reproducible cell type compositions that are conserved upon extended culture. We expect that application of this method will provide new insights into brain development and disease processes.
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