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Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models.

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Bossi, Beatrice 
Conforti, Paola 
Galimberti, Maura 
Dezi, Fabio 


In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.


Peer reviewed: True


brain regional identity, cell type specificity, default and directed differentiation protocols, hPSC-derived 3D brain organoid models, neuronal maturation, Humans, Organoids, Pluripotent Stem Cells, Cell Differentiation, Neurons, Brain

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Int J Mol Sci

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European Commission (602278)
European Commission (305121)
Medical Research Council (MC_PC_17230)