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  • 1
    Publication Date: 2011-05-10
    Description: 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273988/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273988/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bendall, Sean C -- Simonds, Erin F -- Qiu, Peng -- Amir, El-ad D -- Krutzik, Peter O -- Finck, Rachel -- Bruggner, Robert V -- Melamed, Rachel -- Trejo, Angelica -- Ornatsky, Olga I -- Balderas, Robert S -- Plevritis, Sylvia K -- Sachs, Karen -- Pe'er, Dana -- Tanner, Scott D -- Nolan, Garry P -- 1R01CA130826/CA/NCI NIH HHS/ -- 272200700038C/PHS HHS/ -- 5U54 CA143907/CA/NCI NIH HHS/ -- HHSN268201000034C/HV/NHLBI NIH HHS/ -- N0I-HV-00242/HV/NHLBI NIH HHS/ -- P01 CA034233/CA/NCI NIH HHS/ -- PN2 EY018228/EY/NEI NIH HHS/ -- R01 CA130826/CA/NCI NIH HHS/ -- R01 CA130826-04/CA/NCI NIH HHS/ -- RB2-01592/PHS HHS/ -- U19 AI057229/AI/NIAID NIH HHS/ -- U54 CA149145/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2011 May 6;332(6030):687-96. doi: 10.1126/science.1198704.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21551058" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Antibodies ; Antigens, Surface/analysis ; B-Lymphocytes/drug effects/immunology/metabolism ; Bone Marrow Cells/cytology/*drug effects/*immunology/metabolism ; Cytokines/metabolism ; Dasatinib ; Flow Cytometry/*methods ; Hematopoiesis ; Humans ; Immunophenotyping ; Lanthanoid Series Elements ; Leukocytes, Mononuclear/drug effects/immunology/metabolism ; Lymphocyte Activation ; Lymphocyte Subsets/*drug effects/*immunology/metabolism ; Mass Spectrometry ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Pyrimidines/*pharmacology ; *Signal Transduction/drug effects ; Single-Cell Analysis/*methods ; T-Lymphocytes/drug effects/immunology/metabolism ; Thiazoles/*pharmacology ; Transition Elements
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-07-15
    Description: Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537647/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537647/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spitzer, Matthew H -- Gherardini, Pier Federico -- Fragiadakis, Gabriela K -- Bhattacharya, Nupur -- Yuan, Robert T -- Hotson, Andrew N -- Finck, Rachel -- Carmi, Yaron -- Zunder, Eli R -- Fantl, Wendy J -- Bendall, Sean C -- Engleman, Edgar G -- Nolan, Garry P -- 1R01CA130826/CA/NCI NIH HHS/ -- 1R01GM109836/GM/NIGMS NIH HHS/ -- 1R01NS089533/NS/NINDS NIH HHS/ -- 1U19AI100627/AI/NIAID NIH HHS/ -- 201303028/PHS HHS/ -- 5-24927/PHS HHS/ -- 5R01AI073724/AI/NIAID NIH HHS/ -- 5U54CA143907/CA/NCI NIH HHS/ -- 7500108142/PHS HHS/ -- F31 CA189331/CA/NCI NIH HHS/ -- F31CA189331/CA/NCI NIH HHS/ -- F32 GM093508/GM/NIGMS NIH HHS/ -- F32 GM093508-01/GM/NIGMS NIH HHS/ -- HHSF223201210194C/PHS HHS/ -- HHSN268201000034C/HV/NHLBI NIH HHS/ -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272201200028C/PHS HHS/ -- K99 GM104148/GM/NIGMS NIH HHS/ -- K99GM104148-01/GM/NIGMS NIH HHS/ -- N01-HV-00242/HV/NHLBI NIH HHS/ -- P01 CA034233/CA/NCI NIH HHS/ -- P01 CA034233-22A1/CA/NCI NIH HHS/ -- PN2 EY018228/EY/NEI NIH HHS/ -- PN2EY018228 0158 G KB065/EY/NEI NIH HHS/ -- R01 AI073724/AI/NIAID NIH HHS/ -- R01 CA130826/CA/NCI NIH HHS/ -- R01 CA184968/CA/NCI NIH HHS/ -- R01 GM109836/GM/NIGMS NIH HHS/ -- R01 NS089533/NS/NINDS NIH HHS/ -- R01CA184968/CA/NCI NIH HHS/ -- R33 CA183654/CA/NCI NIH HHS/ -- R33 CA183692/CA/NCI NIH HHS/ -- RFA CA 09-009/CA/NCI NIH HHS/ -- RFA CA 09-011/CA/NCI NIH HHS/ -- T32 GM007276/GM/NIGMS NIH HHS/ -- T32GM007276/GM/NIGMS NIH HHS/ -- U19 AI057229/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 CA149145/CA/NCI NIH HHS/ -- U54CA149145/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):1259425. doi: 10.1126/science.1259425.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Department of Pathology, Stanford University, Stanford, CA 94305, USA. Program in Immunology, Stanford University, Stanford, CA 94305, USA. gnolan@stanford.edu matthew.spitzer@stanford.edu. ; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. ; Department of Pathology, Stanford University, Stanford, CA 94305, USA. ; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Program in Immunology, Stanford University, Stanford, CA 94305, USA. ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University, Stanford, CA 94305, USA. ; Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Program in Immunology, Stanford University, Stanford, CA 94305, USA. gnolan@stanford.edu matthew.spitzer@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26160952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow/immunology ; Circadian Rhythm/immunology ; Flow Cytometry ; Genetic Variation ; Humans ; Immune System/*cytology/*immunology ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Phenotype ; Reference Standards
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
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