Single-cell multiomics reveals a shared regulatory program in progenitor CD8 T cells and follicular helper CD4 T cell during viral infection

To explore potential regulatory functions that might be shared by different populations of T cells, we generated a new single-cell multiomic (scRNA-seq + scATAC-seq) data for CD4 and CD8 T cells responding to acute and chronic viral infection. By integrating this new dataset with a compendium of 285 published bulk ATAC-seq datasets, we were able to identify all major T cell states, including naive, memory, effector, follicular helper (Tfh), regulatory, exhausted and progenitor populations, across both infection contexts.

Archetypal analysis revealed regulatory programs that were driven by distinct transcription factors acting across multiple T cell subsets. Our work provides a broadly applicable framework and a valuable resource for dissecting transcriptional control mechanisms in adaptive immune responses.