Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [single cell RNA-Seq]

The thymus is the site of T cell development. Although much is known about the development and differentiation of the T lymphocyte compartment, less is known about the thymic epithelial cell (TEC) populations fostering their development. Here we use next generation sequencing approaches to identify transcriptional programs unique to TEC at specific stages of mouse life. This strategy identified Myc as a regulator of the fetal program, driving the rapid expansion in thymic size during fetal life. Next-generation sequencing approaches on a large data set enabled the identification of age-specific transcriptional programs; and established a key role for Myc in driving TEC proliferation, ribosomal biogenesis, and regulating thymic size.胸腺是T细胞发育的核心场所。尽管学界对T淋巴细胞谱系的发育与分化机制已有较为深入的认识，但对介导T细胞发育的胸腺上皮细胞（thymic epithelial cell, TEC）亚群的了解仍相对有限。本研究采用下一代测序（next generation sequencing, NGS）技术，鉴定小鼠生命周期特定阶段中TEC特有的转录程序。该策略发现Myc基因作为胎儿期转录程序的调控因子，可驱动胎儿发育阶段胸腺体积的快速扩增。基于大型数据集的下一代测序分析进一步鉴定出年龄特异性的转录程序，并证实Myc在介导TEC增殖、核糖体生物发生以及调控胸腺体积方面发挥关键作用。