Lineage recording in human cerebral organoids.
IF: 47.990
Cited by: 64


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.


Spatial Transcriptomics


He, Zhisong
Maynard, Ashley
Jain, Akanksha
Gerber, Tobias
Petri, Rebecca
Lin, Hsiu-Chuan
Santel, Malgorzata
Ly, Kevin
Dupré, Jean-Samuel
Sidow, Leila
Sanchis Calleja, Fatima
Jansen, Sophie M J
Riesenberg, Stephan
Camp, J Gray
Treutlein, Barbara

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