Generation of human cerebral organoids with a structured outer subventricular zone Journal Article
| Authors: | Walsh, R. M.; Luongo, R.; Giacomelli, E.; Ciceri, G.; Rittenhouse, C.; Verrillo, A.; Galimberti, M.; Bocchi, V. D.; Wu, Y.; Xu, N.; Mosole, S.; Muller, J.; Vezzoli, E.; Jungverdorben, J.; Zhou, T.; Barker, R. A.; Cattaneo, E.; Studer, L.; Baggiolini, A. |
| Article Title: | Generation of human cerebral organoids with a structured outer subventricular zone |
| Abstract: | Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The oSVZ comprises progenitor cells expressing specific oRG markers such as GFAP, LIFR, and HOPX, closely matching human fetal oRG. Finally, incorporating neural crest-derived LIF-producing cortical pericytes into cortical organoids recapitulates the effects of LIF treatment. These data indicate that increasing the cellular complexity of the organoid microenvironment promotes the emergence of oRG and supports a platform to study oRG in hPSC-derived brain organoids routinely. © 2024 The Author(s) |
| Keywords: | immunohistochemistry; signal transduction; unclassified drug; human cell; gene; stat3 protein; embryonic stem cell; glial fibrillary acidic protein; transcription factor; subventricular zone; immunofluorescence; enzyme linked immunosorbent assay; histology; stem cell; western blotting; blood brain barrier; cell migration; neocortex; neural crest; pluripotent stem cell; microenvironment; nerve cell differentiation; nestin; fluorescence activated cell sorting; electrophysiology; transcription factor sox2; protein cdc42; mitochondrial respiration; pericyte; lif; leukemia inhibitory factor; mammalian target of rapamycin complex 1; gene ontology; choroid plexus; human pluripotent stem cells; pericytes; human; male; female; article; outer subventricular zone; hek293t cell line; cerebral organoid; hpsc; single cell rna seq; mitochondrial gene; outer radial glia; cp: neuroscience; cp: stem cell research; cortical assembloids; hpsc-derived brain organoids; org; osvz; disks large homolog 4; t box brain transcription factor 1; cortical organoid; hopx gene; lifr gene; patch clamp technique |
| Journal Title: | Cell Reports |
| Volume: | 43 |
| Issue: | 4 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2024-04-23 |
| Start Page: | 114031 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2024.114031 |
| PROVIDER: | scopus |
| PUBMED: | 38583153 |
| PMCID: | PMC11322983 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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