Early transcriptional and epigenetic regulation of CD8(+) T cell differentiation revealed by single-cell RNA sequencing.
Early transcriptional and epigenetic regulation of CD8(+) T cell differentiation revealed by single-cell RNA sequencing.
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DOI：
10.1038/ni.3688
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发表时间：
2017-04
影响因子：
30.5
通讯作者：
Yeo GW
中科院分区：
文献类型：
--
作者：
Kakaradov B;Arsenio J;Widjaja CE;He Z;Aigner S;Metz PJ;Yu B;Wehrens EJ;Lopez J;Kim SH;Zuniga EI;Goldrath AW;Chang JT;Yeo GW
在微生物感染期间，做出反应的 CD8+ T 淋巴细胞分化为异质亚群，这些亚群共同提供即时且持久的保护。为了阐明这一过程中的动态转录变化，我们应用了单细胞 RNA 测序方法，并在体内病毒感染过程中连续分析了单个 CD8+ T 淋巴细胞。我们的分析揭示了经历第一次分裂的细胞之间存在显着的转录差异，并确定了以前未知的控制 CD8+ T 淋巴细胞命运规范的分子决定因素。这些发现提出了一种终末效应细胞分化模型，该模型由转录活性的早期爆发启动，随后通过与记忆淋巴细胞相关的转录物的表观遗传沉默来完善，强调了单细胞方法的力量和必要性。
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 controlling CD8+ T lymphocyte fate specification. These findings suggest a model of terminal effector cell differentiation initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, highlighting the power and necessity of single-cell approaches.