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

Thymic-derived Treg cells consist of heterogeneous subsets with different characteristics and development. Overall design: 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.