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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Book
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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.