Recent evidence has elucidated how multipotent blood progenitors transform their identities in the thymus and undergo commitment to become T cells. Together with environmental signals, a core group of transcription factors have essential roles in this process by directly activating and repressing specific genes. Many of these transcription factors also function in later T cell development, but control different genes. Here, we review how these transcription factors work to change the activities of specific genomic loci during early intrathymic development to establish T cell lineage identity. We introduce the key regulators and highlight newly emergent insights into the rules that govern their actions. Whole-genome deep sequencing-based analysis has revealed unexpectedly rich relationships between inherited epigenetic states, transcription factor–DNA binding affinity thresholds and influences of given transcription factors on the activities of other factors in the same cells. Together, these mechanisms determine T cell identity and make the lineage choice irreversible.

最近的证据阐明了多能血液祖细胞如何在胸腺中转变其身份并承诺成为 T 细胞。与环境信号一起，一组核心转录因子通过直接激活和抑制特定基因在此过程中发挥重要作用。其中许多转录因子也在 T 细胞后期发育中发挥作用，但控制不同的基因。在这里，我们回顾了这些转录因子如何在早期胸腺发育过程中改变特定基因组位点的活性，从而建立 T 细胞谱系特性。我们介绍了主要监管机构，并重点介绍了对其行为规则的新见解。基于全基因组深度测序的分析揭示了遗传性表观遗传状态、转录因子-DNA结合亲和力阈值以及给定转录因子对同一细胞中其他因子活性的影响之间出乎意料的丰富关系。这些机制共同决定了 T 细胞的身份并使谱系选择不可逆转。