Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 51, Pages 15672-15677Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1520760112
Keywords
cerebral organoid; neocortex; corticogenesis; single-cell RNA-seq; stem cells
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Funding
- Austrian Academy of Sciences
- Austrian Science Fund [I_552-B19, Z_153_B09]
- European Research Council (ERC)
- Allen Family Foundation
- Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich 655]
- ERC [250197]
- DFG
- Fonds der Chemischen Industrie
- MRC [MC_UP_1201/9] Funding Source: UKRI
- Austrian Science Fund (FWF) [Z 153] Funding Source: researchfish
- Medical Research Council [MC_UP_1201/9] Funding Source: researchfish
- Austrian Science Fund (FWF) [Z153] Funding Source: Austrian Science Fund (FWF)
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Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying
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