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  Lineage recording in human cerebral organoids

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.

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Creators

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 Creators:
He, Zhisong, Author
Maynard, Ashley, Author
Jain, Akanksha, Author
Gerber, Tobias1, 2, 3, Author                 
Petri, Rebecca, Author
Lin, Hsiu-Chuan, Author
Santel, Malgorzata, Author
Ly, Kevin, Author
Dupré, Jean-Samuel, Author
Sidow, Leila4, Author                 
Sanchis Calleja, Fatima, Author
Jansen, Sophie M. J., Author
Riesenberg, Stephan1, 3, Author                 
Camp, J. Gray, Author
Treutlein, Barbara1, 2, 5, Author                 
Affiliations:
1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_1497672              
2Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_2173644              
3The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_1497688              
4Modern and Archaic Human Cell Biology, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_2477693              
5Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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Free keywords: Gene expression, Neurogenesis, RNA sequencing, Stem-cell differentiation
 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.

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Language(s): eng - English
 Dates: 2022-01
 Publication Status: Issued
 Pages: 31
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41592-021-01344-8
 Degree: -

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Title: Nature Methods
Source Genre: Journal
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Pages: - Volume / Issue: 19 (1) Sequence Number: - Start / End Page: 90 - 99 Identifier: ISSN: 1548-7105