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      High-dimensional, single-cell characterization of the brain's immune compartment

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          Colony-stimulating factors in inflammation and autoimmunity.

          John Hamilton (2008)
          Although they were originally defined as haematopoietic-cell growth factors, colony-stimulating factors (CSFs) have been shown to have additional functions by acting directly on mature myeloid cells. Recent data from animal models indicate that the depletion of CSFs has therapeutic benefit in many inflammatory and/or autoimmune conditions and as a result, early-phase clinical trials targeting granulocyte/macrophage colony-stimulating factor and macrophage colony-stimulating factor have now commenced. The distinct biological features of CSFs offer opportunities for specific targeting, but with some associated risks. Here, I describe these biological features, discuss the probable specific outcomes of targeting CSFs in vivo and highlight outstanding questions that need to be addressed.
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            Extracting a Cellular Hierarchy from High-dimensional Cytometry Data with SPADE

            Peng-Fei Qiu, Erin Simonds, Sean Bendall … (2011)
            Multiparametric single-cell analysis is critical for understanding cellular heterogeneity. Despite recent technological advances in single-cell measurements, methods for analyzing high-dimensional single-cell data are often subjective, labor intensive and require prior knowledge of the biological system under investigation. To objectively uncover cellular heterogeneity from single-cell measurements, we present a novel computational approach, Spanning-tree Progression Analysis of Density-normalized Events (SPADE). We applied SPADE to cytometry data of mouse and human bone marrow. In both cases, SPADE organized cells in a hierarchy of related phenotypes that partially recapitulated well-described patterns of hematopoiesis. In addition, SPADE produced a map of intracellular signal activation across the landscape of human hematopoietic development. SPADE revealed a functionally distinct cell population, natural killer (NK) cells, without using any NK-specific parameters. SPADE is a versatile method that facilitates the analysis of cellular heterogeneity, the identification of cell types, and comparison of functional markers in response to perturbations.
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              Heterogeneity of CNS myeloid cells and their roles in neurodegeneration.

              Marco Prinz, Josef Priller, Sangram Sisodia … (2011)
              The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epitope expression. However, recent data suggest that resident microglia may be functionally distinct from bone marrow- or blood-derived phagocytes, which invade the CNS under pathological conditions. During the last few years, research on brain myeloid cells has been markedly changed by the advent of new tools in imaging, genetics and immunology. These methodologies have yielded unexpected results, which challenge the traditional view of brain macrophages. On the basis of these new studies, we differentiate brain myeloid subtypes with regard to their origin, function and fate in the brain and illustrate the divergent features of these cells during neurodegeneration. © 2011 Nature America, Inc. All rights reserved.
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                Author and article information

                Journal
                Title: Nature Neuroscience
                Abbreviated Title: Nat Neurosci
                Publisher: Springer Nature
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Created: July 24 2017
                Publication date (Print): July 24 2017
                Volume:
                Issue:
                Article
                DOI: 10.1038/nn.4610
                PubMed ID: 28758994
                SO-VID: 128f786f-08d1-41db-bf9e-3b13557e2ee0
                Copyright © © 2017
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