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Nat Immunol. 2017 Apr;18(4):422-432. doi: 10.1038/ni.3688. Epub 2017 Feb 20.

Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing.

Author information

1
Department of Cellular and Molecular Medicine, University of California, San Diego, California, USA.
2
Department of Medicine, University of California, San Diego, California, USA.
3
Division of Biological Sciences, University of California, San Diego, California, USA.
4
Institute for Genomic Medicine, University of California, San Diego, California, USA.
5
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

During microbial infection, responding CD8+ T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8+ T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8+ T lymphocytes. Our findings suggest a model for the differentiation of terminal effector cells initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, which highlights the power and necessity of single-cell approaches.

PMID:
28218746
PMCID:
PMC5360497
DOI:
10.1038/ni.3688
[Indexed for MEDLINE]
Free PMC Article

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