Per-cell histone acetylation is associated with terminal differentiation in human T cells.
Clin Epigenetics
; 16(1): 21, 2024 02 06.
Article
en En
| MEDLINE
| ID: mdl-38321550
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Histonas
/
Metilación de ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Epigenetics
Año:
2024
Tipo del documento:
Article
País de afiliación:
China