小柯机器人

中国科学院脑科学与智能技术卓越创新中心陈跃军等研究人员合作实现克隆谱系在人类神经分化发育阶段的映射。该项研究成果于2023年3月17日在线发表在《细胞—干细胞》杂志上。

研究人员开发了单细胞分离条形码（SISBAR）技术，可以在人类腹侧中脑-后脑分化的体外模型中对单细胞转录组进行跨阶段的克隆追踪。研究人员开发了“潜在视角”和“起源视角”分析，以研究跨阶段的系谱关系，并绘制了描绘整个分化过程的多层次克隆系谱图。研究人员发现了许多以前未被描述的汇聚和分化的轨迹。此外，研究人员证明了一个转录组定义的细胞类型可以从不同的谱系中产生，这些谱系在它们的后代中留下了分子印记，一个祖细胞类型的多谱系命运代表了不同的而非单个祖细胞的类似克隆命运的集体结果，每个祖细胞都有不同的分子特征。

具体来说，研究人员发现腹侧中脑祖细胞群是中脑多巴胺能（mDA）神经元、中脑谷氨酸能神经元、血管和脑膜细胞的共同克隆起源，并确定了一个可以改善移植结果的表面标记。

附：英文原文

Title: Mapping of clonal lineages across developmental stages in human neural differentiation

Author: Zhiwen You, Luyue Wang, Hui He, Ziyan Wu, Xinyue Zhang, Shuaixiang Xue, Peibo Xu, Yanhong Hong, Man Xiong, Wu Wei, Yuejun Chen

Issue&Volume: 2023-03-17

Abstract: 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.

DOI: 10.1016/j.stem.2023.02.007

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

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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