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

Jinmiao Chen (), Andreas Schlitzer, Svetoslav Chakarov, Florent Ginhoux and Michael Poidinger
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Jinmiao Chen: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03-06, Singapore 138648, Singapore
Andreas Schlitzer: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03-06, Singapore 138648, Singapore
Svetoslav Chakarov: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03-06, Singapore 138648, Singapore
Florent Ginhoux: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03-06, Singapore 138648, Singapore
Michael Poidinger: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03-06, Singapore 138648, Singapore

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms11988

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