美国加州大学Aaron Streets、Nir Yosef和Ellen A. Robey研究组合作利用胸腺细胞发育的单细胞多组学分析揭示了CD4+ T细胞和CD8+ T细胞谱系定型的驱动因素。相关论文于2023年8月14日发表在《自然—免疫学》杂志上。

他们应用CITE-seq来检测野生型和T细胞谱系限制小鼠胸腺细胞中的RNA和表面蛋白，以生成每个T细胞谱系的细胞状态的综合时间表。这些分析确定了一个连续的过程，即所有胸腺细胞在第一波TCR信号传导过程中启动CD4+ T细胞谱系分化，随后是与CD8+ T细胞谱系特化相一致的第二波T细胞抗原受体(TCR)信号传导。CITE-seq和药物抑制实验提示TCR -钙调磷酸酶- NFAT–GATA3轴驱动CD4+ T细胞的命运。他们的数据为理解细胞命运决定提供了资源，并暗示了指导谱系选择的顺序选择过程。

据了解，胸腺中CD4+ T细胞和CD8+ T细胞的发育对适应性免疫至关重要，并作为谱系承诺的一种模式被广泛研究。TCR对自身肽主要组织相容性复合体(MHC) I类或II类的识别分别决定了CD8+或CD4+ T细胞谱系的选择，但TCR信号如何驱动谱系承诺的转录程序仍然很大程度上未知。

附：英文原文

Title: Single-cell multiomic analysis of thymocyte development reveals drivers of CD4+ T cell and CD8+ T cell lineage commitment

Author: Steier, Zo, Aylard, Dominik A., McIntyre, Laura L., Baldwin, Isabel, Kim, Esther Jeong Yoon, Lutes, Lydia K., Ergen, Can, Huang, Tse-Shun, Robey, Ellen A., Yosef, Nir, Streets, Aaron

Issue&Volume: 2023-08-14

Abstract: The development of CD4+ T cells and CD8+ T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-peptide major histocompatibility complex (MHC) class I or II by the T cell antigen receptor (TCR) determines the CD8+ or CD4+ T cell lineage choice, respectively, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. Here we applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and T cell lineage-restricted mice to generate a comprehensive timeline of cell states for each T cell lineage. These analyses identified a sequential process whereby all thymocytes initiate CD4+ T cell lineage differentiation during a first wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8+ T cell lineage specification. CITE-seq and pharmaceutical inhibition experiments implicated a TCR–calcineurin–NFAT–GATA3 axis in driving the CD4+ T cell fate. Our data provide a resource for understanding cell fate decisions and implicate a sequential selection process in guiding lineage choice.

DOI: 10.1038/s41590-023-01584-0

Source: https://www.nature.com/articles/s41590-023-01584-0