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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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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author 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.
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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.
author_sort Lummertz da Rocha, Edroaldo
collection MIT
description 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.
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spelling mit-1721.1/1175892022-10-03T10:48:50Z Reconstruction of complex single-cell trajectories using CellRouter 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. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Synthetic Biology Center Collins, James J. 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. National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24DK092760) National Institute of Allergy and Infectious Diseases (U.S.) (Grant R37AI039394) National Heart, Lung, and Blood Institute (Grant UO1-HL100001) 2018-08-28T16:17:04Z 2018-08-28T16:17:04Z 2018-03 2017-11 2018-08-27T18:13:24Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/117589 Lummertz da Rocha, Edroaldo, et al. “Reconstruction of Complex Single-Cell Trajectories Using CellRouter.” Nature Communications 9, 1 (March 2018): 892 © 2018 The Author(s) https://orcid.org/0000-0002-5560-8246 http://dx.doi.org/10.1038/S41467-018-03214-Y Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature
spellingShingle 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.
Reconstruction of complex single-cell trajectories using CellRouter
title Reconstruction of complex single-cell trajectories using CellRouter
title_full Reconstruction of complex single-cell trajectories using CellRouter
title_fullStr Reconstruction of complex single-cell trajectories using CellRouter
title_full_unstemmed Reconstruction of complex single-cell trajectories using CellRouter
title_short Reconstruction of complex single-cell trajectories using CellRouter
title_sort reconstruction of complex single cell trajectories using cellrouter
url http://hdl.handle.net/1721.1/117589
https://orcid.org/0000-0002-5560-8246
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