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Long-term maturation of human cortical organoids matches key early postnatal transitions
- Source :
- Nature neuroscience
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Human stem-cell-derived models provide the promise of accelerating our understanding of brain disorders, but not knowing whether they possess the ability to mature beyond mid- to late-fetal stages potentially limits their utility. We leveraged a directed differentiation protocol to comprehensively assess maturation in vitro. Based on genome-wide analysis of the epigenetic clock and transcriptomics, as well as RNA editing, we observe that three-dimensional human cortical organoids reach postnatal stages between 250 and 300 days, a timeline paralleling in vivo development. We demonstrate the presence of several known developmental milestones, including switches in the histone deacetylase complex and NMDA receptor subunits, which we confirm at the protein and physiological levels. These results suggest that important components of an intrinsic in vivo developmental program persist in vitro. We further map neurodevelopmental and neurodegenerative disease risk genes onto in vitro gene expression trajectories to provide a resource and webtool (Gene Expression in Cortical Organoids, GECO) to guide disease modeling.
- Subjects :
- 0301 basic medicine
General Neuroscience
Induced Pluripotent Stem Cells
Gene regulatory network
Cell Differentiation
Neurodegenerative Diseases
DNA Methylation
In Vitro Techniques
Biology
Article
Organoids
Transcriptome
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Directed differentiation
RNA editing
Gene expression
Histone deacetylase complex
Organoid
Humans
Gene Regulatory Networks
Epigenetics
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15461726 and 10976256
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....dad37eaa18a89e9ac307bdc0e419f7d7