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  1. Article ; Online: Metacells untangle large and complex single-cell transcriptome networks

    Mariia Bilous / Loc Tran / Chiara Cianciaruso / Aurélie Gabriel / Hugo Michel / Santiago J. Carmona / Mikael J. Pittet / David Gfeller

    BMC Bioinformatics, Vol 23, Iss 1, Pp 1-

    2022  Volume 24

    Abstract: Abstract Background Single-cell RNA sequencing (scRNA-seq) technologies offer unique opportunities for exploring heterogeneous cell populations. However, in-depth single-cell transcriptomic characterization of complex tissues often requires profiling ... ...

    Abstract Abstract Background Single-cell RNA sequencing (scRNA-seq) technologies offer unique opportunities for exploring heterogeneous cell populations. However, in-depth single-cell transcriptomic characterization of complex tissues often requires profiling tens to hundreds of thousands of cells. Such large numbers of cells represent an important hurdle for downstream analyses, interpretation and visualization. Results We develop a framework called SuperCell to merge highly similar cells into metacells and perform standard scRNA-seq data analyses at the metacell level. Our systematic benchmarking demonstrates that metacells not only preserve but often improve the results of downstream analyses including visualization, clustering, differential expression, cell type annotation, gene correlation, imputation, RNA velocity and data integration. By capitalizing on the redundancy inherent to scRNA-seq data, metacells significantly facilitate and accelerate the construction and interpretation of single-cell atlases, as demonstrated by the integration of 1.46 million cells from COVID-19 patients in less than two hours on a standard desktop. Conclusions SuperCell is a framework to build and analyze metacells in a way that efficiently preserves the results of scRNA-seq data analyses while significantly accelerating and facilitating them.
    Keywords Single-cell transcriptomics ; Computational biology ; Coarse-graining ; Metacells ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A durable murine model of spleen transplantation with arterial and venous anastomoses

    Jose-Luiz Figueiredo / Fernando Santa-Cruz / José Luiz Lima-Filho / Ingo Hilgendorf / Masanori Aikawa / Mikael J. Pittet / Matthias Nahrendorf / Ralph Weissleder / Filip K. Swirski / Clinton S. Robbins

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 7

    Abstract: Abstract The spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. ... ...

    Abstract Abstract The spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. This is due, in large part, to a lack of in vivo, spleen-specific lineage tagging strategies. Here, we describe a detailed practical protocol of spleen transplantation and its evaluation for long-term graft survival. Unlike implantation of splenic morsels in the great omentum, our approach uses arterial and venous anastomoses which rapidly restores blood flow and facilitates long-term survival of the graft. The use of congenic mouse strains permits the use of immunofluorescence and flow cytometry-based methodologies to unambiguously track the migration of spleen-derived cells to peripheral tissues.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Tumor-Promoting Ly-6G+ SiglecFhigh Cells Are Mature and Long-Lived Neutrophils

    Christina Pfirschke / Camilla Engblom / Jeremy Gungabeesoon / Yunkang Lin / Steffen Rickelt / Rapolas Zilionis / Marius Messemaker / Marie Siwicki / Genevieve M. Gerhard / Anna Kohl / Etienne Meylan / Ralph Weissleder / Allon M. Klein / Mikael J. Pittet

    Cell Reports, Vol 32, Iss 12, Pp 108164- (2020)

    2020  

    Abstract: Summary: Myeloid cells co-expressing the markers CD11b, Ly-6G, and SiglecF can be found in large numbers in murine lung adenocarcinomas and accelerate cancer growth by fostering tumor cell invasion, angiogenesis, and immunosuppression; however, some of ... ...

    Abstract Summary: Myeloid cells co-expressing the markers CD11b, Ly-6G, and SiglecF can be found in large numbers in murine lung adenocarcinomas and accelerate cancer growth by fostering tumor cell invasion, angiogenesis, and immunosuppression; however, some of these cells’ fundamental features remain unexplored. Here, we show that tumor-infiltrating CD11b+ Ly-6G+ SiglecFhigh cells are bona fide mature neutrophils and therefore differ from other myeloid cells, including SiglecFhigh eosinophils, SiglecFhigh macrophages, and CD11b+ Ly-6G+ myeloid-derived suppressor cells. We further show that SiglecFhigh neutrophils gradually accumulate in growing tumors, where they can live for several days; this lifespan is in marked contrast to that of their SiglecFlow counterparts and neutrophils in general, which live for several hours only. Together, these findings reveal distinct attributes for tumor-promoting SiglecFhigh neutrophils and help explain their deleterious accumulation in the tumor bed.
    Keywords neutrophils ; cancer ; myeloid cells ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging

    Michael F. Cuccarese / J. Matthew Dubach / Christina Pfirschke / Camilla Engblom / Christopher Garris / Miles A. Miller / Mikael J. Pittet / Ralph Weissleder

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 10

    Abstract: Tumour-associated macrophages (TAM) can be used as prognostic indicators in cancer. Here, the authors establish a platform for high-throughput 3D microscopy in murine lung carcinoma that allows to visualize TAMs infiltration throughout the entire lung, ... ...

    Abstract Tumour-associated macrophages (TAM) can be used as prognostic indicators in cancer. Here, the authors establish a platform for high-throughput 3D microscopy in murine lung carcinoma that allows to visualize TAMs infiltration throughout the entire lung, response to CSF-1R blockade and nanoparticle drug delivery.
    Keywords Science ; Q
    Language English
    Publishing date 2017-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects

    Hsin-Wei Liao / Christopher Garris / Christina Pfirschke / Steffen Rickelt / Sean Arlauckas / Marie Siwicki / Rainer H. Kohler / Ralph Weissleder / Vibeke Sundvold-Gjerstad / Baldur Sveinbjørnsson / Øystein Rekdal / Mikael J. Pittet

    Cell Stress, Vol 3, Iss 11, Pp 348-

    2019  Volume 360

    Abstract: LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer ... ...

    Abstract LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound antitumor effects against Braf- and Pten-driven melanoma and delays the progression of Kras- and P53-driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of lymphocytes. The second phase of response, which continues over weeks, is defined by long-term alteration of the tumor microenvironment; the changes induced by LTX-315 are most notably characterized by CD8+ T cell infiltration. We further show that these CD8+ T cells are involved in suppressing melanoma outgrowth in mice and report similar CD8+ T cell infiltration following LTX-315 treatment in melanoma and sarcoma patients. Taken together, these findings reveal LTX-315’s multiple antitumor effects, including disrupting the tumor vasculature and promoting the conversion of poorly immunogenic tumors into ones that display antitumor T cell immunity.
    Keywords cancer ; immunotherapy ; oncolytic peptide ; cd8+ t cells ; melanoma ; sarcoma ; Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Shared Science Publishers OG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Durable and controlled depletion of neutrophils in mice

    Gael Boivin / Julien Faget / Pierre-Benoit Ancey / Aspasia Gkasti / Julie Mussard / Camilla Engblom / Christina Pfirschke / Caroline Contat / Justine Pascual / Jessica Vazquez / Nathalie Bendriss-Vermare / Christophe Caux / Marie-Catherine Vozenin / Mikael J. Pittet / Matthias Gunzer / Etienne Meylan

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new ... ...

    Abstract Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.
    Keywords Science ; Q
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Durable and controlled depletion of neutrophils in mice

    Gael Boivin / Julien Faget / Pierre-Benoit Ancey / Aspasia Gkasti / Julie Mussard / Camilla Engblom / Christina Pfirschke / Caroline Contat / Justine Pascual / Jessica Vazquez / Nathalie Bendriss-Vermare / Christophe Caux / Marie-Catherine Vozenin / Mikael J. Pittet / Matthias Gunzer / Etienne Meylan

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new ... ...

    Abstract Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.
    Keywords Science ; Q
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: PF4 Promotes Platelet Production and Lung Cancer Growth

    Ferdinando Pucci / Steffen Rickelt / Andita P. Newton / Christopher Garris / Ernesto Nunes / Charles Evavold / Christina Pfirschke / Camilla Engblom / Mari Mino-Kenudson / Richard O. Hynes / Ralph Weissleder / Mikael J. Pittet

    Cell Reports, Vol 17, Iss 7, Pp 1764-

    2016  Volume 1772

    Abstract: Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, ... ...

    Abstract Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis. Additionally, anti-platelet treatment controlled mouse lung cancer progression, further suggesting that platelets can modulate the tumor microenvironment to accelerate tumor outgrowth. These findings support PF4 as a cancer-enhancing endocrine signal that controls discrete aspects of bone marrow hematopoiesis and tumor microenvironment and that should be considered as a molecular target in anticancer therapy.
    Keywords Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

    Ken S Lau / Virna Cortez-Retamozo / Sarah R Philips / Mikael J Pittet / Douglas A Lauffenburger / Kevin M Haigis

    PLoS Biology, Vol 10, Iss 9, p e

    2012  Volume 1001393

    Abstract: Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to ... ...

    Abstract Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting.
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Correction

    Ken S. Lau / Virna Cortez-Retamozo / Sarah R. Philips / Mikael J. Pittet / Douglas A. Lauffenburger / Kevin M. Haigis

    PLoS Biology, Vol 10, Iss

    Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium.

    2012  Volume 10

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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