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Mapping of clonal lineages across developmental stages in human neural differentiation

ABSTRACT: The cell lineages across developmental stages remains to be elucidated. We developed single-cell split barcoding (SISBAR) to allow clonally tracking single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We developed “potential-spective” and “origin-spective” analysis to interrogate the cross-stage lineage relationships, and mapped a multi-level clonal lineage landscape depicting the whole differentiation process. We uncovered many previously uncharacterized converging and diverging trajectories. We demonstrated that a transcriptome-defined cell type can arise from distinct lineages that leave molecular imprints on their progenies, and the multi-lineage fates of a progenitor cell type represent the collective results of distinct rather than similar clonal fates of individual progenitors, each with distinct molecular signatures. Specifically, we uncovered a ventral midbrain progenitor cluster as the common clonal origin of midbrain dopaminergic (mDA) neurons, midbrain glutamatergic neurons, and vascular and leptomeningeal cells, and identified surface markers that can predict its lineage fate after transplantation and improve graft outcomes.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE207921 | GEO | 2022/07/12

REPOSITORIES: GEO

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Mapping of clonal lineages across developmental stages in human neural differentiation (Biological Replicates #2 and #3)

Project description:The cell lineages across developmental stages remains to be elucidated. We developed single-cell split barcoding (SISBAR) to allow clonally tracking single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We developed “potential-spective” and “origin-spective” analysis to interrogate the cross-stage lineage relationships, and mapped a multi-level clonal lineage landscape depicting the whole differentiation process. We uncovered many previously uncharacterized converging and diverging trajectories. We demonstrated that a transcriptome-defined cell type can arise from distinct lineages that leave molecular imprints on their progenies, and the multi-lineage fates of a progenitor cell type represent the collective results of distinct rather than similar clonal fates of individual progenitors, each with distinct molecular signatures. Specifically, we uncovered a ventral midbrain progenitor cluster as the common clonal origin of midbrain dopaminergic (mDA) neurons, midbrain glutamatergic neurons, and vascular and leptomeningeal cells, and identified surface markers that can predict its lineage fate after transplantation and improve graft outcomes.

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