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Single-cell gene expression analysis reveals regulators of distinct cell subpopulations among developing human neurons

    • 1Stem Cell and Regenerative Biology, Genome Institute of Singapore/A-STAR, Singapore 138672;
    • 2Genome and Gene expression Data Analysis Division, Bioinformatics Institute, Singapore 138671;
    • 3Luxembourg Centre for Systems Biomedicine, Campus Belval, University of Luxembourg, L-4367 Luxembourg;
    • 4Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    • 5 These authors contributed equally to this work.
    • Present addresses: 6Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; 7Living Systems Institute, University of Exeter, Exeter EX4 4SB, UK; 8Cancer Science Institute, National University of Singapore, Singapore 117599; 9Humacyte, Inc., Durham, NC 27709, USA
Published October 13, 2017. Vol 27 Issue 11, pp. 1783-1794. https://doi.org/10.1101/gr.223313.117
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Abstract

The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of developing neurons to dissect/identify NPC subtypes and critical developmental stages of alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell developmental bifurcations, tracking the stochastic transcript kinetics of the subpopulations, elucidating regulatory networks, and finding key regulators. Our data revealed the bifurcation and developmental tracks of the two NPC subpopulations, and we captured an early (24 h) transition phase that leads to alternative neuronal specifications. The consequent up-regulation and down-regulation of stage- and subpopulation-specific gene groups during the course of maturation revealed biological insights with regard to key regulatory transcription factors and lincRNAs that control cellular programs in the identified neuronal subpopulations.

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