Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development.

Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development.
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DOI:
10.1038/ncomms11988
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发表时间:
2016-06-30
影响因子:
16.6
通讯作者:
Poidinger M
Poidinger M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen J;Schlitzer A;Chakarov S;Ginhoux F;Poidinger M

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单细胞rna测序提供了细胞分化和发育过程中连续状态转变的前所未有的解决方案。然而,从单细胞数据构建多分支细胞谱系的工具是有限的。在这里,我们提出了Mpath,一种使用基于邻居的细胞状态转换派生多分支发展轨迹的算法。Mpath应用于小鼠常规树突状细胞(cDC)祖细胞,构建了从巨噬细胞/DC祖细胞到普通DC祖细胞到前树突状细胞(preDC)的多分支轨迹。path生成的轨迹检测了preDC阶段的分支事件,揭示了专门致力于cDC1或cDC2谱系的preDC子集。在cDC发育过程中对细胞进行重排序,揭示了细胞周期与cDC分化之间的基因调控序列和时间耦合。应用于人成肌细胞,Mpath重现了成肌细胞分化的时间过程,并分离出参与分化的非肌肉细胞分支。我们的研究表明,Mpath是从单细胞数据构建细胞谱系的有用工具。从单细胞数据构建细胞谱系的工具是有限的。在这里,作者提出了Mpath:一种使用基于邻居的细胞状态转换来导出多分支轨迹的算法,并使用它来预测树突状细胞和肌肉细胞的发育轨迹。
Single-cell RNA-sequencing offers unprecedented resolution of the continuum of state transition during cell differentiation and development. However, tools for constructing multi-branching cell lineages from single-cell data are limited. Here we present Mpath, an algorithm that derives multi-branching developmental trajectories using neighborhood-based cell state transitions. Applied to mouse conventional dendritic cell (cDC) progenitors, Mpath constructs multi-branching trajectories spanning from macrophage/DC progenitors through common DC progenitor to pre-dendritic cells (preDC). The Mpath-generated trajectories detect a branching event at the preDC stage revealing preDC subsets that are exclusively committed to cDC1 or cDC2 lineages. Reordering cells along cDC development reveals sequential waves of gene regulation and temporal coupling between cell cycle and cDC differentiation. Applied to human myoblasts, Mpath recapitulates the time course of myoblast differentiation and isolates a branch of non-muscle cells involved in the differentiation. Our study shows that Mpath is a useful tool for constructing cell lineages from single-cell data. The tools for constructing cell lineages from single cell data are limited. Here, the authors present Mpath: an algorithm to derive multi-branching trajectories using neighbourhood-based cell state transitions, and use this to predict developmental trajectories in dendritic and muscle cells.