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Journal Article

Lineage recording in human cerebral organoids

MPS-Authors
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Gerber,  Tobias       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

/persons/resource/persons211028

Sidow,  Leila       
Modern and Archaic Human Cell Biology, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

/persons/resource/persons192484

Riesenberg,  Stephan       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

/persons/resource/persons179767

Treutlein,  Barbara       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society;

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Fulltext (public)

He_Lineage_NatMet_2022.pdf
(Publisher version), 20MB

Supplementary Material (public)

He_Lineage_NatMet_Suppl_2022.pdf
(Supplementary material), 2MB

He_Lineage_NatMet_Suppl2_2022.tsv
(Supplementary material), 3KB

He_Lineage_NatMet_Suppl3_2022.tsv
(Supplementary material), 8MB

He_Lineage_NatMet_Suppl4_2022.tsv
(Supplementary material), 3MB

He_Lineage_NatMet_Suppl5_2022.tsv
(Supplementary material), 2MB

He_Lineage_NatMet_Suppl6_2022.tsv
(Supplementary material), 4KB

He_Lineage_NatMet_Suppl7_2022.xlsx
(Supplementary material), 117KB

He_Lineage_NatMet_Suppl8_2022.tsv
(Supplementary material), 126KB

He_Lineage_NatMet_Suppl9_2022.xlsx
(Supplementary material), 67KB

Citation

He, Z., Maynard, A., Jain, A., Gerber, T., Petri, R., Lin, H.-C., et al. (2022). Lineage recording in human cerebral organoids. Nature Methods, 19(1), 90-99. doi:10.1038/s41592-021-01344-8.


Cite as: https://hdl.handle.net/21.11116/0000-0009-C4DE-0
Abstract
Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enable highly resolved descriptions of cell states within these systems; however, approaches are needed to directly measure lineage relationships. Here we establish iTracer, a lineage recorder that combines reporter barcodes with inducible CRISPR–Cas9 scarring and is compatible with single-cell and spatial transcriptomics. We apply iTracer to explore clonality and lineage dynamics during cerebral organoid development and identify a time window of fate restriction as well as variation in neurogenic dynamics between progenitor neuron families. We also establish long-term four-dimensional light-sheet microscopy for spatial lineage recording in cerebral organoids and confirm regional clonality in the developing neuroepithelium. We incorporate gene perturbation (iTracer-perturb) and assess the effect of mosaic TSC2 mutations on cerebral organoid development. Our data shed light on how lineages and fates are established during cerebral organoid formation. More broadly, our techniques can be adapted in any iPSC-derived culture system to dissect lineage alterations during normal or perturbed development.