Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models.
Manuela MagniBeatrice BossiPaola ConfortiMaura GalimbertiFabio DeziTiziana LischettiXiaoling HeRoger A BarkerChiara ZuccatoIra Espuny-CamachoElena CattaneoPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- resting state
- cerebral ischemia
- functional connectivity
- pluripotent stem cells
- single cell
- white matter
- endothelial cells
- induced apoptosis
- subarachnoid hemorrhage
- poor prognosis
- spinal cord
- type diabetes
- cell proliferation
- gene expression
- brain injury
- metabolic syndrome
- spinal cord injury
- cell therapy
- neuropathic pain
- skeletal muscle
- cell cycle arrest
- transcription factor
- endoplasmic reticulum stress