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Developmental Origin Governs CD8+ T Cell Fate Decisions during Infection.

Norah L Smith | Ravi K Patel | Arnold Reynaldi | Jennifer K Grenier | Jocelyn Wang | Neva B Watson | Kito Nzingha | Kristel J Yee Mon | Seth A Peng | Andrew Grimson | Miles P Davenport | Brian D Rudd
Cell | 2018

Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8+ T cell pool that are distinguished by their developmental origin, unique transcriptional profiles, distinct chromatin landscapes, and different kinetics and phenotypes after microbial challenge. These data demonstrate that the naive CD8+ T cell pool is not as homogeneous as previously thought and offers a new framework for explaining the remarkable heterogeneity in the effector and memory T cell subsets that arise after infection.

Pubmed ID: 29909981

Antibodies used in this publication

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI105265
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI110613
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI131348
  • Agency: NICHD NIH HHS, United States
    Id: P50 HD076210

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This is a list of tools and resources that we have found mentioned in this publication.


UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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Subread (tool)

RRID:SCR_009803

Software package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.

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SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

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Morpheus by Broad Institute (tool)

RRID:SCR_017386

Software tool for versatile matrix visualization and analysis. Program to generate heatmaps from input data. JavaScript matrix visualization and analysis.

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FITC anti-mouse CD103 (antibody)

RRID:AB_10714791

This monoclonal targets CD103

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B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (organism)

RRID:IMSR_JAX:006148

Mus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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BiNGO: A Biological Networks Gene Ontology tool (software resource)

RRID:SCR_005736

The Biological Networks Gene Ontology tool (BiNGO) is an open-source Java tool to determine which Gene Ontology (GO) terms are significantly overrepresented in a set of genes. BiNGO can be used either on a list of genes, pasted as text, or interactively on subgraphs of biological networks visualized in Cytoscape. BiNGO maps the predominant functional themes of the tested gene set on the GO hierarchy, and takes advantage of Cytoscape''''s versatile visualization environment to produce an intuitive and customizable visual representation of the results. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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B6.SJL-PtprcaPepc/BoyCrCrl (organism)

RRID:IMSR_CRL:564

Mus musculus with name B6.SJL-PtprcaPepc/BoyCrCrl from IMSR.

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TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

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Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

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cutadapt (software resource)

RRID:SCR_011841

Software tool that removes adapter sequences from DNA sequencing reads.

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Cytoscape (software resource)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J (organism)

RRID:IMSR_JAX:007909

Mus musculus with name B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J from IMSR.

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GOrilla: Gene Ontology Enrichment Analysis and Visualization Tool (service resource)

RRID:SCR_006848

A tool for identifying and visualizing enriched GO terms in ranked lists of genes. It can be run in one of two modes: * Searching for enriched GO terms that appear densely at the top of a ranked list of genes or * Searching for enriched GO terms in a target list of genes compared to a background list of genes.

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edgeR (software resource)

RRID:SCR_012802

Bioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.

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B6(129X1)-Tg(Cd4-cre/ERT2)11Gnri/J (organism)

RRID:IMSR_JAX:022356

Mus musculus with name B6(129X1)-Tg(Cd4-cre/ERT2)11Gnri/J from IMSR.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Cufflinks (software resource)

RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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BEDTools (software resource)

RRID:SCR_006646

A powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.

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featureCounts (software resource)

RRID:SCR_012919

A read summarization program, which counts mapped reads for the genomic features such as genes and exons.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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Qvalue (software resource)

RRID:SCR_001073

R package that takes a list of p-values resulting from the simultaneous testing of hypotheses and estimates their q-values. It is designed to measure the proportion of false positives when a test is significant. The software is capable of generating plots for visualization. It can be applied to problems in genomics, brain imaging, astrophysics, and data mining.

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B6.PL-Thy1a/CyJ (organism)

RRID:IMSR_JAX:000406

Mus musculus with name B6.PL-Thy1a/CyJ from IMSR.

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