PDF(Pubmed)
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.
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.
摘要：
背景：据报道，效应基因位点的表观遗传重塑在调节T细胞分化和功能方面至关重要。然而,研究控制T细胞行为的潜在表观遗传机制的努力在很大程度上受到非常有限的实验工具的阻碍，尤其是在人类中。
结果：在这项研究中，我们采用流式细胞术分析人T细胞中单细胞水平的组蛋白乙酰化.数据显示组蛋白乙酰化在T细胞活化期间增加。在T细胞亚群中，将强力产生效应细胞因子的终末分化效应记忆T(TEMRA)细胞超乙酰化。相反，这些TEMRA细胞的TCF-1表达水平较低,TCF-1是维持干细胞特征的关键转录因子.使用小分子C646对组蛋白乙酰化的药物抑制抑制效应分子的产生，但在扩增后保留了T细胞的干细胞样特性。
结论：每细胞组蛋白乙酰化与人T细胞的终末分化和干细胞性差相关。这些观察表明了一种新的方法来增强T细胞的干细胞样特性并提高免疫疗法的功效。
结果：在这项研究中，我们采用流式细胞术分析人T细胞中单细胞水平的组蛋白乙酰化.数据显示组蛋白乙酰化在T细胞活化期间增加。在T细胞亚群中，将强力产生效应细胞因子的终末分化效应记忆T(TEMRA)细胞超乙酰化。相反，这些TEMRA细胞的TCF-1表达水平较低,TCF-1是维持干细胞特征的关键转录因子.使用小分子C646对组蛋白乙酰化的药物抑制抑制效应分子的产生，但在扩增后保留了T细胞的干细胞样特性。
结论：每细胞组蛋白乙酰化与人T细胞的终末分化和干细胞性差相关。这些观察表明了一种新的方法来增强T细胞的干细胞样特性并提高免疫疗法的功效。
