Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum
Sean C. Bendall,Erin F. Simonds,Peng Qiu,El-ad David Amir,Peter O. Krutzik,Rachel Finck,Robert V. Bruggner,Rachel D. Melamed,Angelica Trejo,Olga Ornatsky,Robert S. Balderas,Sylvia K. Plevritis,Karen Sachs,Dana Pe'er,Scott D. Tanner,Garry P. Nolan +15 more
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TLDR
Single-cell “mass cytometry” 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.Abstract:
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.read more
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TL;DR: 66 In the version of this article initially published in print and online, the authors did not include acknowledgements of grant support as required by their funding policies.
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References
More filters
疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
The green fluorescent protein
TL;DR: In just three years, the green fluorescent protein from the jellyfish Aequorea victoria has vaulted from obscurity to become one of the most widely studied and exploited proteins in biochemistry and cell biology.
Journal ArticleDOI
A quantitative analysis of kinase inhibitor selectivity.
Mazen W. Karaman,Sanna Herrgard,Daniel K. Treiber,Paul Gallant,Corey E. Atteridge,Brian T. Campbell,Katrina W Chan,Pietro Ciceri,Mindy I. Davis,Philip T. Edeen,Raffaella Faraoni,Mark Floyd,Jeremy P. Hunt,Daniel J Lockhart,Zdravko V. Milanov,Michael J Morrison,Gabriel Pallares,Hitesh K. Patel,Stephanie Pritchard,Stephanie Pritchard,Lisa M. Wodicka,Patrick P. Zarrinkar +21 more
TL;DR: This work presents interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome and introduces the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns.
Book
Practical Flow Cytometry
TL;DR: Using Flow Cytometers: Applications, Extensions, and Alternatives as mentioned in this paper is an excellent overview of the history of the field of Flow Sorting, its applications, extensions, and alternatives.
Journal ArticleDOI
Causal Protein-Signaling Networks Derived from Multiparameter Single-Cell Data
Karen Sachs,Karen Sachs,Karen Sachs,Omar D. Perez,Omar D. Perez,Omar D. Perez,Dana Pe'er,Dana Pe'er,Dana Pe'er,Douglas A. Lauffenburger,Douglas A. Lauffenburger,Douglas A. Lauffenburger,Garry P. Nolan,Garry P. Nolan,Garry P. Nolan +14 more
TL;DR: Reconstruction of network models from physiologically relevant primary single cells might be applied to understanding native-state tissue signaling biology, complex drug actions, and dysfunctional signaling in diseased cells.