Mass Cytometry as a Tool for Investigating Senescence in Multiple Model Systems.
Mass Cytometry as a Tool for Investigating Senescence in Multiple Model Systems.
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DOI：
10.3390/cells12162045
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发表时间：
2023-08-11
期刊：
影响因子：
6
通讯作者：
Behbehani, Gregory K.
中科院分区：
文献类型：
--
作者：
Abdul-Aziz, Amina;Devine, Raymond D.;Lyberger, Justin M.;Chang, Hsiaochi;Kovacs, Amy;Lerma, James R.;Rogers, Andrew M.;Byrd, John C.;Hertlein, Erin;Behbehani, Gregory K.
细胞衰老是由于细胞增殖能力有限而导致的持久的细胞周期停滞。衰老对内在和外在的细胞应激都有反应，例如衰老、线粒体功能障碍、辐射和化疗。在这里，我们报告了使用质量流式细胞术 (MC) 来分析多个模型系统，并证明 MC 作为单细胞水平衰老分析的平台。我们在几个已建立的衰老模型系统中并使用分离的人类 T 细胞证明了 p16 表达、细胞周期分数和组蛋白尾部修饰的变化。在骨髓间充质基质细胞 (BMSC) 中，我们发现随着后续传代，p16 表达增加，循环细胞和开放染色质标记减少。在 WI-38 细胞中，我们证明 p16 表达随着培养诱导的衰老和氧化应激诱导的衰老 (OSIS) 的增加而增加。我们还使用 Wanderlust（一种轨迹分析工具）来演示 p16 表达如何随组蛋白尾部修饰和细胞周期蛋白而变化。最后，我们证明用 CD3/CD28 珠重复刺激人类 T 细胞会诱导 p16 表达增加的耗尽表型。这个表达 p16 的群体表现出较高的耗竭标记（如 EOMES 和 TOX）表达。这项工作表明，MC 是在单细胞蛋白质水平上研究衰老的有用平台，并且能够以高置信度同时测量多个衰老标志物，从而提高我们对衰老途径的理解。
Cellular senescence is a durable cell cycle arrest as a result of the finite proliferative capacity of cells. Senescence responds to both intrinsic and extrinsic cellular stresses, such as aging, mitochondrial dysfunction, irradiation, and chemotherapy. Here, we report on the use of mass cytometry (MC) to analyze multiple model systems and demonstrate MC as a platform for senescence analysis at the single-cell level. We demonstrate changes to p16 expression, cell cycling fraction, and histone tail modifications in several established senescent model systems and using isolated human T cells. In bone marrow mesenchymal stromal cells (BMSCs), we show increased p16 expression with subsequent passage as well as a reduction in cycling cells and open chromatin marks. In WI-38 cells, we demonstrate increased p16 expression with both culture-induced senescence and oxidative stress-induced senescence (OSIS). We also use Wanderlust, a trajectory analysis tool, to demonstrate how p16 expression changes with histone tail modifications and cell cycle proteins. Finally, we demonstrate that repetitive stimulation of human T cells with CD3/CD28 beads induces an exhausted phenotype with increased p16 expression. This p16-expressing population exhibited higher expression of exhaustion markers such as EOMES and TOX. This work demonstrates that MC is a useful platform for studying senescence at a single-cell protein level, and is capable of measuring multiple markers of senescence at once with high confidence, thereby improving our understanding of senescent pathways.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
DOI：
10.1093/gerona/glaa108
发表时间：
2020-12-01
影响因子：
5.1
作者：
Burd, Christin E.;Peng, Juan;Kiecolt-Glaser, Janice K.
通讯作者：
Kiecolt-Glaser, Janice K.
DOI：
10.1126/science.1198704
发表时间：
2011-05-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bendall SC;Simonds EF;Qiu P;Amir el-AD;Krutzik PO;Finck R;Bruggner RV;Melamed R;Trejo A;Ornatsky OI;Balderas RS;Plevritis SK;Sachs K;Pe'er D;Tanner SD;Nolan GP
通讯作者：
Nolan GP
DOI：
10.1007/978-1-4939-7371-2_8
发表时间：
2018-01-01
期刊：
CELLULAR QUIESCENCE: METHODS AND PROTOCOLS
影响因子：
--
作者：
Behbehani, Gregory K.
通讯作者：
Behbehani, Gregory K.
影响因子：
16.6
作者：
Belkina, Anna C.;Ciccolella, Christopher O.;Snyder-Cappione, Jennifer E.
通讯作者：
Snyder-Cappione, Jennifer E.