Mapping of clonal lineages across developmental stages in human neural differentiation

• DOI: 10.1016/j.stem.2023.02.007
• Publication Date: 2023-03-17T15:19:09Z
• Authors: Zhiwen You; Luyue Wang; Hui He; Ziyan Wu; Xinyue Zhang; Shuaixiang Xue; Peibo Xu; Yanhong Hong; Man Xiong; Wu Wei; Yuejun Chen
• Keywords: Hindbrain; Lineage (genetic); Progenitor; Cell type

The cell lineages across developmental stages remain to be elucidated. Here, we developed single-cell split barcoding (SISBAR) that allows clonal tracking of transcriptomes in an vitro model human ventral midbrain-hindbrain differentiation. We "potential-spective" and "origin-spective" analyses investigate the cross-stage lineage relationships mapped a multi-level landscape depicting whole differentiation process. uncovered many previously uncharacterized converging diverging trajectories. Furthermore, demonstrate transcriptome-defined type can arise from distinct leave molecular imprints on their progenies, multilineage fates progenitor cell-type represent collective results rather than similar individual progenitors, each with signatures. Specifically, midbrain cluster as common origin dopaminergic (mDA) neurons, glutamatergic vascular leptomeningeal cells identified surface marker improve graft outcomes.