AI Article Synopsis
- Organoids (ORGs) serve as effective models for studying cerebral cortical development compared to monolayers (MONs) derived from the same stem cell lines.
- MONs showed increased cell proliferation due to enhanced integrin signaling but displayed issues with radial glia polarity and Notch signaling, leading to reduced production of key brain cell types.
- The study indicates that ORGs maintain better cell adhesion and efficient Notch signaling, resulting in a more accurate reproduction of the developmental process in the cortex compared to MONs.
Article Abstract
Organoids (ORGs) are increasingly used as models of cerebral cortical development. Here, we compared transcriptome and cellular phenotypes between telencephalic ORGs and monolayers (MONs) generated in parallel from three biologically distinct induced pluripotent stem cell (iPSC) lines. Multiple readouts revealed increased proliferation in MONs, which was caused by increased integrin signaling. MONs also exhibited altered radial glia (RG) polarity and suppression of Notch signaling, as well as impaired generation of intermediate progenitors, outer RG, and cortical neurons, which were all partially reversed by reaggregation of dissociated cells. Network analyses revealed co-clustering of cell adhesion, Notch-related transcripts and their transcriptional regulators in a module strongly downregulated in MONs. The data suggest that ORGs, with respect to MONs, initiate more efficient Notch signaling in ventricular RG owing to preserved cell adhesion, resulting in subsequent generation of intermediate progenitors and outer RG, in a sequence that recapitulates the cortical ontogenetic process.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878838 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2020.12.019 | DOI Listing |
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