Development of high-throughput lineage tracing tools and exploration of the developmental mechanisms of stem/progenitor cells

The cell lineages across developmental stages remain to be elucidated. Here, we developed single-cell split barcoding (SISBAR) that allows clonal tracking of single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We uncovered many previously uncharacterized converging and diverging trajectories, demonstrating that a transcriptome-defined cell type can arise from distinct lineages, and the multilineage fates of a progenitor cell-type is the collective results of distinct clonal fates of individual progenitors. Specifically, we uncovered a ventral midbrain progenitor cluster as the clonal origin of midbrain dopaminergic (mDA) neurons and identified a surface marker that can improve graft outcomes.

Key article:
https://www.sciencedirect.com/science/article/pii/S1934590923000449