Robust Production of Uniform Human Cerebral Organoids from Pluripotent Stem Cells
Robust Production of Uniform Human Cerebral Organoids from Pluripotent Stem Cells
Abstract Human cerebral organoid (hCO) models offer the opportunity to understand fundamental processes underlying human specific cortical development and pathophysiology in an experimentally tractable system. While 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 directly addressed this problem by establishing a robust production pipeline to generate morphologically consistent (ie uniform) 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.
Hernandez J. J.、Beaulieu J. M.、Attisano L.、Evstratova A.、Ghoshal B.、Gosio J.T.、Wrana J. L.、Ghiasiighorveh P.、Sivitilli A.、Trcka D.
Department of Molecular Genetics, University of Toronto||Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Pharmacology and Toxicology, University of TorontoDepartment of Biochemistry, University of Toronto||Donnelly Centre, University of TorontoDepartment of Pharmacology and Toxicology, University of TorontoCenter for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Molecular Genetics, University of Toronto||Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Molecular Genetics, University of Toronto||Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai HospitalDepartment of Biochemistry, University of Toronto||Donnelly Centre, University of TorontoDepartment of Biochemistry, University of Toronto||Donnelly Centre, University of TorontoDepartment of Molecular Genetics, University of Toronto||Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
基础医学细胞生物学分子生物学
Hernandez J. J.,Beaulieu J. M.,Attisano L.,Evstratova A.,Ghoshal B.,Gosio J.T.,Wrana J. L.,Ghiasiighorveh P.,Sivitilli A.,Trcka D..Robust Production of Uniform Human Cerebral Organoids from Pluripotent Stem Cells[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.03.08.979013.点此复制
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