Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum.
Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum.
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DOI：
10.1126/science.1198704
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发表时间：
2011-05-06
期刊：
影响因子：
--
通讯作者：
Nolan GP
中科院分区：
文献类型：
--
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
流式细胞术是解剖造血功能复杂性的重要工具。我们使用单细胞“质量细胞术”来检查健康人骨髓，同时测量单细胞中的34个参数（31种抗体的结合、活力、DNA含量和相对细胞大小）。用18种同时存在的功能性信号传导状态的标记物监测跨越限定的造血层级的细胞亚群的信号传导行为，所述标记物被一组离体刺激物和抑制剂干扰。该数据集允许由表面抗原表达定义的相关细胞类型的算法驱动的组装，提供细胞信号传导反应与药物抑制组合的可重叠图。以这种方式可视化，分析揭示了以前未被认识到的精确信号传导反应的实例，这些信号传导反应在常规定义的细胞亚群内有界，并且以意想不到的方式跨越细胞群体边界的更连续的磷酸化反应与细胞表型密切相关。总的来说，这种单细胞分析提供了健康人类造血中免疫信号传导的全系统视图，可以将药物作用和疾病进行比较，以进行机制研究和药理学干预。
Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell “mass cytometry” to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.
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影响因子：
56.9
作者：
FULWYLER, MJ
通讯作者：
FULWYLER, MJ
影响因子：
3.7
作者：
Autissier, Patrick;Soulas, Caroline;Williams, Kenneth C.
通讯作者：
Williams, Kenneth C.
影响因子：
56.9
作者：
KRASNOW, MA;CUMBERLEDGE, S;NOLAN, GP
通讯作者：
NOLAN, GP
DOI：
10.1007/978-3-642-01222-8_7
发表时间：
2010-01-01
期刊：
SMALL MOLECULES IN ONCOLOGY
影响因子：
--
作者：
Lindauer, Markus;Hochhaus, Andreas
通讯作者：
Hochhaus, Andreas
影响因子：
50.3
作者：
Kotecha N;Flores NJ;Irish JM;Simonds EF;Sakai DS;Archambeault S;Diaz-Flores E;Coram M;Shannon KM;Nolan GP;Loh ML
通讯作者：
Loh ML