Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4(+) T Cells in Early Human Pregnancy.
Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4(+) T Cells in Early Human Pregnancy.
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人类妊娠早期蜕膜 CD4( ) T 细胞的独特转录和选择性剪接特征。
DOI：
10.3389/fimmu.2017.00682
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发表时间：
2017
影响因子：
7.3
通讯作者：
Lin Y
中科院分区：
文献类型：
--
作者：
Zeng W;Liu Z;Liu X;Zhang S;Khanniche A;Zheng Y;Ma X;Yu T;Tian F;Liu XR;Fan J;Lin Y
蜕膜CD4 + T（dCD4 T）细胞对于健康妊娠结局所必需的母胎免疫耐受至关重要。然而，它们的分子和功能特性尚未得到很好的阐明。在本研究中，我们利用高通量mRNA测序首次对人类早孕时成对的蜕膜和外周血CD4 + T（pCD4 T）细胞的转录和可变剪接（AS）情况进行了分析。我们的数据显示，与pCD4 T细胞相比，dCD4 T细胞具有独特的转录特征：dCD4 T细胞上调1695个富集于免疫系统过程的基因，而下调1011个主要与mRNA分解代谢过程和核糖体相关的基因。此外，观察到dCD4 T细胞处于M期，并且显示出活化、增殖和细胞因子产生增加，以及呈现效应记忆表型和包含Th1、Th17和Treg细胞亚群的异质性。然而，dCD4 T细胞发生的上调和下调的AS事件数量相当，这两种事件都富集于与细胞代谢过程相关的基因。并且AS事件水平的变化并未反映出dCD4 T细胞在基因表达水平上可测量的差异。总之，我们的研究结果全面描绘了人类蜕膜中CD4 + T细胞独特的转录特征和AS图谱，并帮助我们更好地理解这些细胞在早孕期间的功能特性。
Decidual CD4+ T (dCD4 T) cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS) landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T) cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.