{Reference Type}: Journal Article
{Title}: Per-cell histone acetylation is associated with terminal differentiation in human T cells.
{Author}: Yang C;Li Y;Hu Y;Li Q;Lan Y;Li Y;
{Journal}: Clin Epigenetics
{Volume}: 16
{Issue}: 1
{Year}: 2024 02 6
{Factor}: 7.259
{DOI}: 10.1186/s13148-024-01634-w
{Abstract}: Epigenetic remodeling at effector gene loci has been reported to be critical in regulating T cell differentiation and function. However, efforts to investigate underlying epigenetic mechanisms that control T cell behaviors have been largely hindered by very limited experimental tools, especially in humans.
In this study, we employed a flow cytometric assay to analyze histone acetylation at single-cell level in human T cells. The data showed that histone acetylation was increased during T cell activation. Among T cell subsets, terminally differentiated effector memory T (TEMRA) cells robustly producing effector cytokines were hyper-acetylated. Conversely, these TEMRA cells had lower expression levels of TCF-1, a key transcription factor for maintaining stem cell features. Pharmaceutical inhibition of histone acetylation using a small molecule C646 restrained the production of effector molecules, but retained stem cell-like properties in T cells after expansion.
Per-cell histone acetylation is associated with terminal differentiation and poor stemness in human T cells. These observations suggest a new approach to enhance the stem cell-like properties of T cells and improve the efficacy of immunotherapy.