Cell Stem Cell
Cell Stem Cell
2 years ago

Mapping of clonal lineages across developmental stages in human neural differentiation

Mapping of clonal lineages across developmental stages in human neural differentiation
Zhiwen You, Luyue Wang, Hui He, Ziyan Wu, Xinyue Zhang, Shuaixiang Xue, Peibo Xu, Yanhong Hong, Man Xiong, Wu Wei, Yuejun Chen
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-spective" and "origin-spective" analyses to investigate 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. 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 glutamatergic neurons, and vascular and leptomeningeal cells and identified a surface marker that can improve graft outcomes.

Publisher URL: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00044-9

Open URL: https://doi.org/10.1016/j.stem.2023.02.007

DOI: 10.1016/j.stem.2023.02.007

Open access
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