Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry
Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry
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DOI：
10.1172/jci.insight.128456
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发表时间：
2021-02-22
期刊：
影响因子：
8
通讯作者：
Chheda, Milan G.
中科院分区：
文献类型：
--
作者：
Galdieri, Luciano;Jash, Arijita;Chheda, Milan G.
大多数胶质母细胞瘤(GBM)患者在2年内死亡。一个主要的治疗目标是靶向GBM干细胞(GSCs)，这是一种有助于治疗耐药和复发的细胞亚群。自从2003年发现GSC以来，已经使用CD15、CD44、CD133和a 6整合素等单表面标记分离了GSC。目前尚不清楚这些单表面标记定义的GSC群体在信号和功能方面如何相互比较，以及这些标记的不同组合是否与不同的功能能力相关。利用质谱仪和新鲜的手术室标本，我们在患者中发现了15个不同的GSC亚群，他们的MEK/ERK、WNT和AKT通路的激活状态不同。一旦进入培养阶段，一些亚群就消失了，以前检测不到的亚群出现了。高表达4种表面标志物的GSCs具有最强的自我更新能力、WNT抑制剂敏感性和体内致瘤性。这项工作突出了GSCs潜在的信号和表型多样性。要证实这些发现，需要更大的患者样本量和抗体面板。
Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and a 6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings.