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Epigenetic profiling of human CD4+ memory T cells reveals their proliferative history and argues in favor of a progressive differentiation model driven by epigenetically controlled master regulators.

A key element of adaptive immunity is the development of long-lived memory cells, which protect against recurring infection by providing a highly enriched pool of antigen-specific cells ready to react to the pathogen. Different classes of memory T cells occur upon primary activation of naive T cells, however, their detailed differentiation pathway is not entirely clear. As part of the IHEC consortium, we generated genome-wide epigenetic maps of a number of CD4+ T cell memory (Tmem) stages including rare subsets such as terminally differentiated (TEMRA) and bone marrow-resident Tmem. We found that CD4+ T cells show progressive global DNA demethylation with differentiation into memory stages, which reflects their proliferative history and likely indicates their decline in differentiation and proliferation potential. Furthermore, transcriptomic profiling combined with co-regulation network analyses arranged different Tmem subsets into a successive differentiation pathway. In addition, we identified a number of epigenetically controlled candidate master regulators for Tmem formation, of which we functionally validated a new methylation-sensitive promoter for the known 'naive-keeper' transcription factor Foxp1. Our study highlights the power of epigenomic datasets in the elucidation of the cellular history but also of the functional potential of T cell populations including the identification of epigenetically controlled master regulators.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001865 Illumina HiSeq 2000 21
Publications Citations
MeDeCom: discovery and quantification of latent components of heterogeneous methylomes.
Genome Biol 18: 2017 55
43
Increased chromatin accessibility facilitates intron retention in specific cell differentiation states.
Nucleic Acids Res 50: 2022 11563-11579
4