The thymus is the primary organ for T-cell development, providing an essential microenvironment consisting of the appropriate cytokine milieu and specialized stromal cells. Thymus-seeding progenitors from circulation immigrate into the thymus and undergo the stepwise T-cell specification, commitment, and selection processes. The transcriptional factors, epigenetic regulators, and signaling pathways involved in the T-cell development have been intensively studied using mouse models. Despite our growing knowledge of T-cell development, major questions remain unanswered regarding the ontogeny and early events of T-cell development at the fetal stage, especially in humans. The recently developed single-cell RNA-sequencing technique provides an ideal tool to investigate the heterogeneity of T-cell precursors and the molecular mechanisms underlying the divergent fates of certain T-cell precursors at the single-cell level. In this review, we aim to summarize the current progress of the study on human thymus organogenesis and thymocyte and thymic epithelial cell development, which is to shed new lights on developing novel strategies for in vitro T-cell regeneration and thymus rejuvenation.

胸腺是T细胞发育的主要器官，它提供了由适当的细胞因子环境和专门的基质细胞组成的基本微环境。循环中播种胸腺的祖细胞迁移到胸腺中，并经历逐步的T细胞规格，定型和选择过程。已经使用小鼠模型深入研究了涉及T细胞发育的转录因子，表观遗传调控因子和信号通路。尽管我们对T细胞发育的了解越来越多，但有关胎儿期T细胞发育的个体发育和早期事件的主要问题仍未得到解答，特别是在人类中。最近开发的单细胞RNA测序技术为研究T细胞前体的异质性以及某些T细胞前体在单细胞水平上发散命运的分子机制提供了理想的工具。在这篇综述中，我们旨在总结人类胸腺器官发生以及胸腺细胞和胸腺上皮细胞发育研究的最新进展，这为开发体外T细胞再生和胸腺再生的新策略提供了新的思路。