Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture
Authors
Madison R. Glass, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Elisa A. Waxman, Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Satoshi Yamashita, Center for Neuroscience Research, Children's National Hospital, Washington, DC, USA.
Michael Lafferty, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alvaro A. Beltran, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tala Farah, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Niyanta K. Patel, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rubal Singla, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nana Matoba, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sara Ahmed, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Mary Srivastava, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Emma Drake, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Liam T. Davis, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Meghana Yeturi, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kexin Sun, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Michael I. Love, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kazue Hashimoto-Torii, Center for Neuroscience Research, Children's National Hospital, Washington, DC, USA; Departments of Pediatrics, and Pharmacology & Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Deborah L. French, Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jason L. Stein, UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: jason_stein@med.unc.edu.
Document Type
Journal Article
Publication Date
9-10-2024
Journal
Stem cell reports
DOI
10.1016/j.stemcr.2024.07.008
Keywords
cortical organoids; neurodevelopment; reproducibility; scRNA-seq; stem cell state; tissue clearing
Abstract
While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types at one site, variability in hCO phenotypes across sites using a harmonized protocol has not yet been evaluated. To determine the cross-site reproducibility of hCO differentiation, three independent research groups assayed hCOs in multiple differentiation replicates from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol across 3 months. hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and expression of metabolism and cellular stress genes. Variability in hCO phenotypes correlated with stem cell gene expression prior to differentiation and technical factors associated with seeding, suggesting iPSC quality and treatment are important for differentiation outcomes. Cross-site reproducibility of hCO cell type proportions and organization encourages future prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.
APA Citation
Glass, Madison R.; Waxman, Elisa A.; Yamashita, Satoshi; Lafferty, Michael; Beltran, Alvaro A.; Farah, Tala; Patel, Niyanta K.; Singla, Rubal; Matoba, Nana; Ahmed, Sara; Srivastava, Mary; Drake, Emma; Davis, Liam T.; Yeturi, Meghana; Sun, Kexin; Love, Michael I.; Hashimoto-Torii, Kazue; French, Deborah L.; and Stein, Jason L., "Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture" (2024). GW Authored Works. Paper 5656.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5656
