The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells

Nature Biotechnology
Cole TrapnellJohn L Rinn

Abstract

Defining the transcriptional dynamics of a temporal process such as cell differentiation is challenging owing to the high variability in gene expression between individual cells. Time-series gene expression analyses of bulk cells have difficulty distinguishing early and late phases of a transcriptional cascade or identifying rare subpopulations of cells, and single-cell proteomic methods rely on a priori knowledge of key distinguishing markers. Here we describe Monocle, an unsupervised algorithm that increases the temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points. Applied to the differentiation of primary human myoblasts, Monocle revealed switch-like changes in expression of key regulatory factors, sequential waves of gene regulation, and expression of regulators that were not known to act in differentiation. We validated some of these predicted regulators in a loss-of function screen. Monocle can in principle be used to recover single-cell gene expression kinetics from a wide array of cellular processes, including differentiation, proliferation and oncogenic transformation.

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Apr 19, 2018·Nature Reviews. Molecular Cell Biology·Blanca Pijuan-SalaBerthold Göttgens
Jun 7, 2018·American Journal of Respiratory and Critical Care Medicine·Wu-Lin ZuoRonald G Crystal
Apr 3, 2018·Nature Biotechnology·Bushra RajAlexander F Schier
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Jun 29, 2018·Bioinformatics·Jie LiuWilliam Stafford Noble
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Dec 7, 2018·JCI Insight·Karolyn A OetjenChristopher S Hourigan
Feb 15, 2019·Frontiers in Genetics·Aanchal MongiaAngshul Majumdar
Nov 11, 2018·Nature Communications·Aashi JindalDebarka Sengupta
Nov 14, 2018·Bioinformatics·Christopher A PenfoldM Azim Surani
Dec 16, 2018·The Journal of Cell Biology·Kenichiro TaniguchiDeborah L Gumucio
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Feb 13, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Satoko SakamotoAkira Watanabe
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Mar 8, 2020·Science Immunology·Marco KünzliCarolyn G King
Jan 11, 2020·Frontiers in Genetics·Jiajun ZhangTianshou Zhou
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Nov 27, 2019·Blood Advances·Catherine Gutierrez, Catherine J Wu
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Feb 9, 2020·Genome Biology·David LähnemannAlexander Schönhuth
Apr 3, 2020·Nature Reviews. Genetics·Daniel E Wagner, Allon M Klein
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