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Cell-to-Cell Adhesion and Neurogenesis in Human Cortical Development: A Study Comparing 2D Monolayers with 3D
Soraya Scuderi1, Giovanna G Altobelli2, Vincenzo Cimini3
1Child Study Center, Yale University, New Haven, CT 06520, USA.
Stem Cell Reports
|January 29, 2021
Summary
Cerebral organoids (ORGs) better model brain development than monolayers (MONs). ORGs promote efficient Notch signaling and neuron generation by preserving cell adhesion, unlike MONs which show altered cell polarity and signaling.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Neuroscience
Background:
- Organoids (ORGs) are advanced models for studying cerebral cortical development.
- Induced pluripotent stem cell (iPSC)-derived monolayers (MONs) offer an alternative but potentially less accurate model.
Purpose of the Study:
- To compare the transcriptome and cellular phenotypes of telencephalic ORGs and MONs.
- To elucidate the mechanisms underlying differences in developmental trajectories between ORGs and MONs.
Main Methods:
- Parallel generation of telencephalic ORGs and MONs from three distinct iPSC lines.
- Transcriptome sequencing and cellular phenotype analysis.
- Network analysis to identify co-regulated gene modules.
Main Results:
- MONs exhibited increased proliferation due to integrin signaling, altered radial glia (RG) polarity, and suppressed Notch signaling.
- MONs showed impaired generation of intermediate progenitors, outer RG, and cortical neurons compared to ORGs.
- Reaggregation of dissociated MON cells partially reversed these developmental defects.
- Network analysis identified a downregulated module in MONs involving cell adhesion and Notch signaling components.
Conclusions:
- Organoids, by preserving cell adhesion, facilitate more efficient Notch signaling in ventricular RG.
- This efficient signaling in ORGs supports the sequential generation of intermediate progenitors and outer RG, recapitulating cortical development.
- Monolayer culture disrupts key signaling pathways and cell-cell interactions crucial for accurate cortical development modeling.
