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Mapping of clonal lineages across developmental in human neural differentiation
论文作者 You, ZW; Wang, LY; He, H; Wu, ZY; Zhang, XY; Xue, SX; Xu, PB; Hong, YH; Xiong, M; Wei, W; Chen, YJ
期刊/会议名称 CELL STEM CELL
论文年度 2023
论文类别 Article
摘要 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 developed potential-spectiveand origin-spectiveanalyses to investigate the cross-stage lineage relationships and mapped a multi-level clonal lineage landscape depicting the whole differentiation process. We uncovered many previously unchar-acterized converging and diverging trajectories. Furthermore, we demonstrate that a transcriptome-defined cell type can arise from distinct lineages that leave molecular imprints on their progenies, and the multilineage 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 glutama-tergic neurons, and vascular and leptomeningeal cells and identified a surface marker that can improve graft outcomes.
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