Reconstruction of complex single-cell trajectories using CellRouter

Edroaldo Lummertz Da Rocha, R. Grant Rowe, Vanessa Lundin, Mohan Malleshaiah, Deepak Kumar Jha, Carlos R. Rambo, Hu Li, Trista E. North, James J. Collins, George Q. Daley

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

A better understanding of the cell-fate transitions that occur in complex cellular ecosystems in normal development and disease could inform cell engineering efforts and lead to improved therapies. However, a major challenge is to simultaneously identify new cell states, and their transitions, to elucidate the gene expression dynamics governing cell-type diversification. Here, we present CellRouter, a multifaceted single-cell analysis platform that identifies complex cell-state transition trajectories by using flow networks to explore the subpopulation structure of multi-dimensional, single-cell omics data. We demonstrate its versatility by applying CellRouter to single-cell RNA sequencing data sets to reconstruct cell-state transition trajectories during hematopoietic stem and progenitor cell (HSPC) differentiation to the erythroid, myeloid and lymphoid lineages, as well as during re-specification of cell identity by cellular reprogramming of monocytes and B-cells to HSPCs. CellRouter opens previously undescribed paths for in-depth characterization of complex cellular ecosystems and establishment of enhanced cell engineering approaches.

Original languageEnglish (US)
Article number892
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Lummertz Da Rocha, E., Rowe, R. G., Lundin, V., Malleshaiah, M., Jha, D. K., Rambo, C. R., Li, H., North, T. E., Collins, J. J., & Daley, G. Q. (2018). Reconstruction of complex single-cell trajectories using CellRouter. Nature communications, 9(1), [892]. https://doi.org/10.1038/s41467-018-03214-y