St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Department of Medicine (St. Vincent's), The University of Melbourne, Fitzroy, Victoria, Australia.
J Immunol. 2021 Jul 15;207(2):363-370. doi: 10.4049/jimmunol.2100408.
T cell development occurs in the thymus, where uncommitted progenitors are directed into a range of sublineages with distinct functions. The goal is to generate a TCR repertoire diverse enough to recognize potential pathogens while remaining tolerant of self. Decades of intensive research have characterized the transcriptional programs controlling critical differentiation checkpoints at the population level. However, greater precision regarding how and when these programs orchestrate differentiation at the single-cell level is required. Single-cell RNA sequencing approaches are now being brought to bear on this question, to track the identity of cells and analyze their gene expression programs at a resolution not previously possible. In this review, we discuss recent advances in the application of these technologies that have the potential to yield unprecedented insight to T cell development.
T 细胞发育发生在胸腺中，未成熟的祖细胞在那里被定向分化为具有不同功能的一系列亚群。其目的是产生多样性足够的 TCR 库，以识别潜在的病原体，同时保持对自身的耐受性。数十年的深入研究已经描述了控制群体水平关键分化检查点的转录程序。然而，需要更高的精度来确定这些程序如何以及何时在单细胞水平上协调分化。单细胞 RNA 测序方法现在正在解决这个问题，以跟踪细胞的身份，并以以前不可能的分辨率分析它们的基因表达程序。在这篇综述中，我们讨论了这些技术的最新应用进展，这些进展有可能为 T 细胞发育提供前所未有的深入见解。
