Human 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, 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 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.

中文翻译：

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T 细胞群转录组变异的荟萃分析揭示了基因表达和剪接的可变和一致特征

人类 T 细胞通常细分为不同的亚型，包括 Th1、Th2、Th17 和 Treg 细胞，它们被认为在体内执行不同的功能。通常，T 细胞亚群由不同基因库的表达定义；然而，关于用于分离的方法和用于定义每个 T 细胞亚型的标记物的研究之间存在差异。因此，如何将研究相互比较仍然是一个悬而未决的问题。此外，之前对 T 细胞亚群中基因表达的分析主要集中在基因表达上，而不是选择性剪接。在这里，我们采用荟萃分析方法，比较人类 Th1、Th2、Th17 和/或 Treg 细胞的 11 项独立 RNA-Seq 研究，以确定跨研究的每个亚型内基因表达和剪接的一致性。我们发现已知的主调节因子始终富含适当的亚型，然而，经常用作标记的细胞因子和其他基因的变化更大。重要的是，我们还确定了以前未知的转录组标记，这些标记似乎始终区分子集，包括一些 Treg 特异性剪接模式。这项工作共同强调了指定为相同亚型的样本之间基因表达的异质性，但也提出了可用于定义功能分组的其他标记。包括一些 Treg 特异性剪接模式。这项工作共同强调了指定为相同亚型的样本之间基因表达的异质性，但也提出了可用于定义功能分组的其他标记。包括一些 Treg 特异性剪接模式。这项工作共同强调了指定为相同亚型的样本之间基因表达的异质性，但也提出了可用于定义功能分组的其他标记。