Multimodal single cell profiling identifies nclTECs and links chromatin remodeling to TEC differentiation and self-antigen expression modes [scMultiome-seq]

Based on differences in chromatin accessibility, we resolve three subpopulations within the previously reported mcTEC progenitor population, and show that differentiation towards mTEC(III) involves chromatin remodelling reminiscent of epidermal differentiation.

Substantial differences in chromatin accessibility are observed across TEC populations at distal regulatory elements, which we hypothesise contribute to stochastic expression of tissue-restricted antigens. Our findings provide insight into mechanisms underlying immunodeficiencies, autoimmune diseases, and certain cancer types, and may inform therapies using engineered or transplanted thymic tissue to induce or enhance T-cell function.