Gene regulatory logic underlying the differentiation of mixed lineages in human thymic epithelial cells

Matched single-cell profiling of 126,687 human thymic epithelial cells identifies 17 TEC subsets defined by distinct expression of 1,843 cell type restricted-antigens from 48 peripheral cell types.

• Why it matters: Human TECs include lineage-committed programs linked to peripheral tissues, but how these programs arise and whether TEC subpopulations are genetically related or conserved in mice is unclear.
• What they did: The study used matched single-cell gene-expression and chromatin-accessibility profiling, then applied a phylogenetic reconstruction method to infer shared ancestry and regulatory control via coordinated activator and repressor regulons.
• The result: Lineage-committed TECs share a common ancestor and retain mixed thymus identity through co-expression of multiple CRA signatures, while mouse TECs use a shared regulatory strategy but conserve few master transcription-factor drivers.

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