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

Author

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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
    Present address: Myeloid Cell Biology, Life & Medical Sciences Institute, University of Bonn, Carl Troll Strasse 31, 53115 Bonn, Germany.)

  • 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)

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.

Suggested Citation

  • Jinmiao Chen & Andreas Schlitzer & Svetoslav Chakarov & Florent Ginhoux & Michael Poidinger, 2016. "Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11988
    DOI: 10.1038/ncomms11988
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    Cited by:

    1. Hao Chen & Mai Chan Lau & Michael Thomas Wong & Evan W Newell & Michael Poidinger & Jinmiao Chen, 2016. "Cytofkit: A Bioconductor Package for an Integrated Mass Cytometry Data Analysis Pipeline," PLOS Computational Biology, Public Library of Science, vol. 12(9), pages 1-17, September.
    2. Eva C. Freckmann & Emma Sandilands & Erin Cumming & Matthew Neilson & Alvaro Román-Fernández & Konstantina Nikolatou & Marisa Nacke & Tamsin R. M. Lannagan & Ann Hedley & David Strachan & Mark Salji &, 2022. "Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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