Reconstruction of complex single-cell trajectories using CellRouter

Nature Communications
Edroaldo Lummertz da RochaGeorge Q Daley

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.

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Citations

Jul 4, 2019·Nature Biotechnology·Melissa A KinneyGeorge Q Daley
Nov 12, 2019·Briefings in Bioinformatics·Wei-Feng GuoLuonan Chen
Jan 3, 2020·Current Opinion in Oncology·Charlotte K Brierley, Adam J Mead
Feb 19, 2020·PLoS Computational Biology·Chieh LinZiv Bar-Joseph
Nov 30, 2018·Frontiers in Immunology·Fatima Valdes-MoraDavid Gallego-Ortega
Apr 27, 2019·Frontiers in Genetics·Geng ChenTieliu Shi
May 6, 2020·Cellular and Molecular Life Sciences : CMLS·Wei GeWei Shen
Jan 11, 2020·Frontiers in Genetics·Jiajun ZhangTianshou Zhou
May 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Peng HuangXiangmin Xu
Aug 10, 2019·World Journal of Stem Cells·Layal El WazanRaymond Ching-Bong Wong
Aug 2, 2019·Current Opinion in Cell Biology·Polina Kameneva, Igor Adameyko
Nov 4, 2020·Neoplasia : an International Journal for Oncology Research·Abicumaran Uthamacumaran
Oct 13, 2018·Trends in Cell Biology·Zi Ye, Casim A Sarkar
Jun 26, 2021·Nature Communications·Robrecht CannoodtYvan Saeys
Jul 27, 2021·Statistical Science : a Review Journal of the Institute of Mathematical Statistics·Y X Rachel WangHaiyan Huang
Sep 14, 2021·Frontiers in Genetics·Yang ChenZhengqing Ouyang

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Datasets Mentioned

BETA
GSE76983
GSE84874
Next
GSE81682
GSE75478
GSE72857
GSE70245
E-MTAB-4079

Methods Mentioned

BETA
RNA-seq
fluorescence-activated cell sorting
PCA

Software Mentioned

Waterfall
CLR
Monocle
R
CellNet
Splatter
DESeq2
PAM
CellRouter
QuantStudio

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