Per-cell histone acetylation is associated with terminal differentiation in human T cells

Autor: Cheng Yang, You Li, Yaqiu Hu, Qian Li, Yinghua Lan, Yongguo Li
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Clinical Epigenetics, Vol 16, Iss 1, Pp 1-10 (2024)
Druh dokumentu: article
ISSN: 1868-7083
DOI: 10.1186/s13148-024-01634-w
Popis: Abstract Background 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. Results 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. Conclusions 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.
Databáze: Directory of Open Access Journals
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