Meta-analysis of transcriptomic variation in T-cell populations reveals both variable and consistent signatures of gene expression and splicing

Human CD4 T cells are often subdivided into distinct subtypes, including Th1, Th2, Th17, and Treg cells, that are thought to carry out distinct functions in the body. Typically, these T-cell subpopulations are defined by the expression of distinct gene repertoires; however, there is variability betw...

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Bibliographic Details
Published in:RNA (Cambridge) 2020-10, Vol.26 (10), p.1320-1333
Main Authors: Radens, Caleb M, Blake, Davia, Jewell, Paul, Barash, Yoseph, Lynch, Kristen W
Format: Article
Language:English
Subjects:
Adult
Alternative splicing
Bioinformatic
CD4 antigen
CD4-Positive T-Lymphocytes - physiology
Cells, Cultured
Cytokines
Cytokines - genetics
Female
Gene expression
Gene Expression - genetics
Helper cells
Humans
Lymphocytes T
Male
Meta-analysis
Middle Aged
Quorum sensing
Ribonucleic acid
RNA
RNA Splicing - genetics
T-Lymphocyte Subsets - physiology
Transcriptome - genetics
Transcriptomics
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Summary:Human CD4 T cells are often subdivided into distinct subtypes, including Th1, Th2, Th17, and Treg cells, that are thought to carry out distinct functions in the body. Typically, these T-cell subpopulations are defined by the expression of distinct gene repertoires; however, there is variability between studies regarding the methods used for isolation and the markers used to define each T-cell subtype. Therefore, how reliably studies can be compared to one another remains an open question. Moreover, previous analysis of gene expression in CD4 T-cell subsets has largely focused on gene expression rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-seq studies of human Th1, Th2, Th17, and/or Treg cells to determine the consistency in gene expression and splicing within each subtype across studies. We find that known master-regulators are consistently enriched in the appropriate subtype; however, cytokines and other genes often used as markers are more variable. Importantly, we also identify previously unknown transcriptomic markers that appear to consistently differentiate between subsets, including a few Treg-specific splicing patterns. Together this work highlights the heterogeneity in gene expression between samples designated as the same subtype, but also suggests additional markers that can be used to define functional groupings.
ISSN:1355-8382
1469-9001
DOI:10.1261/rna.075929.120