Deconstructive SCNT reveals heterogeneity within Treg population [single-cell]

Thymic-derived Treg cells consist of heterogeneous subsets with different characteristics and development. Previously, we used somatic cell nuclear transfer (SCNT) to generate a naturally occurring Treg (nTreg) model. Given our surprising findings relating to the TCR strength of nTreg cells, and the many additional conflicting hypotheses that have evolved around Treg cells, we hypothesized that the Treg population might be heterogeneous and consist of subsets with different characteristics. Hence, we generated another SCNT Treg model, T143. T143 developed in the thymus similar to nTreg T138, but showed evidence of an agonist-induced (aTreg) development contrary to nTreg T138. Strikingly, bulk and single-cell transcriptomic analyses revealed that nTreg T138 and aTreg T143 are two distinct subsets out of four potential Treg subsets.

胸腺来源的调节性T细胞（Thymic-derived Treg cells, Treg）由特征与发育路径各异的异质性亚群组成。此前，我们利用体细胞核移植（Somatic Cell Nuclear Transfer, SCNT）技术构建了天然存在的调节性T细胞（naturally occurring Treg, nTreg）模型。鉴于我们在nTreg细胞的T细胞受体（T Cell Receptor, TCR）信号强度方面取得的意外发现，以及近年来围绕Treg细胞衍生出的诸多相互矛盾的假说，我们推测Treg细胞群体具有异质性，由特征各异的亚群构成。据此，我们构建了另一株SCNT来源的Treg细胞模型T143。T143的胸腺发育过程与nTreg模型T138相似，但其发育路径却呈现出与T138相悖的激动剂诱导的调节性T细胞（agonist-induced Treg, aTreg）发育特征。值得注意的是，批量转录组与单细胞转录组分析结果显示，在四类潜在的Treg细胞亚群中，nTreg T138与aTreg T143属于两个截然不同的亚群。