title: Early transcriptional and epigenetic regulation of CD8+T cell differentiation revealed by single-cell RNA sequencing.
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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, California, USA.
authors.forename: Boyko
authors.initials: B
authors.lastname: Kakaradov
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Janilyn
authors.initials: J
authors.lastname: Arsenio
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Christella E
authors.initials: CE
authors.lastname: Widjaja
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, California, USA.
authors.forename: Zhaoren
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, California, USA.
authors.forename: Stefan
authors.identifier: 0000-0002-9511-3328
authors.initials: S
authors.lastname: Aigner
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Metz
authors.affiliation: Division of Biological Sciences, University of California, San Diego, California, USA.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Yu
authors.affiliation: Division of Biological Sciences, University of California, San Diego, California, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Wehrens
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Lopez
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: Stephanie H
authors.identifier: 0000-0002-8397-1616
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Biological Sciences, University of California, San Diego, California, USA.
authors.forename: Elina I
authors.initials: EI
authors.lastname: Zuniga
authors.affiliation: Division of Biological Sciences, University of California, San Diego, California, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, California, USA.|Institute for Genomic Medicine, University of California, San Diego, California, USA.|Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D020868:Gene Silencing; D018740:Genetic Heterogeneity; D006657:Histones / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D006657:Histones