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

被引:45
作者
Chen, Jinmiao [1 ]
Schlitzer, Andreas [1 ,2 ]
Chakarov, Svetoslav [1 ]
Ginhoux, Florent [1 ]
Poidinger, Michael [1 ]
机构
[1] Agcy Sci Technol & Res, Singapore Immunol Network SIgN, 8A Biomed Grove,03-06, Singapore 138648, Singapore
[2] Univ Bonn, Myeloid Cell Biol Life & Med Sci, Carl Troll Str 31, D-53115 Bonn, Germany
来源
NATURE COMMUNICATIONS | 2016年 / 7卷
关键词
CD8-ALPHA(+) DENDRITIC CELLS; EMBRYONIC STEM-CELLS; RNA-SEQ; EXPRESSION ANALYSES; GENOME-WIDE; DIFFERENTIATION; TRANSCRIPTOMICS; DYNAMICS; LINEAGE; NETWORK;
D O I
10.1038/ncomms11988
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:15
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