Reconstruction of complex single-cell trajectories using CellRouter

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 el...

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Bibliographic Details
Main Authors: Lummertz da Rocha, Edroaldo, Rowe, R. Grant, Lundin, Vanessa, Malleshaiah, Mohan, Jha, Deepak Kumar, Rambo, Carlos R., Li, Hu, North, Trista E., Collins, James J., Daley, George Q.
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Published: Nature Publishing Group 2018
Online Access:http://hdl.handle.net/1721.1/117589
https://orcid.org/0000-0002-5560-8246
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Summary: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.