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  1. Article ; Online: Functional interpretation of single cell similarity maps

    David DeTomaso / Matthew G. Jones / Meena Subramaniam / Tal Ashuach / Chun J. Ye / Nir Yosef

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and ... ...

    Abstract The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and aids interpretation of cellular heterogeneity.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: No detectable alloreactive transcriptional responses under standard sample preparation conditions during donor-multiplexed single-cell RNA sequencing of peripheral blood mononuclear cells

    Christopher S. McGinnis / David A. Siegel / Guorui Xie / George Hartoularos / Mars Stone / Chun J. Ye / Zev J. Gartner / Nadia R. Roan / Sulggi A. Lee

    BMC Biology, Vol 19, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: Abstract Background Single-cell RNA sequencing (scRNA-seq) provides high-dimensional measurements of transcript counts in individual cells. However, high assay costs and artifacts associated with analyzing samples across multiple sequencing runs limit ... ...

    Abstract Abstract Background Single-cell RNA sequencing (scRNA-seq) provides high-dimensional measurements of transcript counts in individual cells. However, high assay costs and artifacts associated with analyzing samples across multiple sequencing runs limit the study of large numbers of samples. Sample multiplexing technologies such as MULTI-seq and antibody hashing using single-cell multiplexing kit (SCMK) reagents (BD Biosciences) use sample-specific sequence tags to enable individual samples to be sequenced in a pooled format, markedly lowering per-sample processing and sequencing costs while minimizing technical artifacts. Critically, however, pooling samples could introduce new artifacts, partially negating the benefits of sample multiplexing. In particular, no study to date has evaluated whether pooling peripheral blood mononuclear cells (PBMCs) from unrelated donors under standard scRNA-seq sample preparation conditions (e.g., 30 min co-incubation at 4 °C) results in significant changes in gene expression resulting from alloreactivity (i.e., response to non-self). The ability to demonstrate minimal to no alloreactivity is crucial to avoid confounded data analyses, particularly for cross-sectional studies evaluating changes in immunologic gene signatures. Results Here, we applied the 10x Genomics scRNA-seq platform to MULTI-seq and/or SCMK-labeled PBMCs from a single donor with and without pooling with PBMCs from unrelated donors for 30 min at 4 °C. We did not detect any alloreactivity signal between mixed and unmixed PBMCs across a variety of metrics, including alloreactivity marker gene expression in CD4+ T cells, cell type proportion shifts, and global gene expression profile comparisons using Gene Set Enrichment Analysis and Jensen-Shannon Divergence. These results were additionally mirrored in publicly-available scRNA-seq data generated using a similar experimental design. Moreover, we identified confounding gene expression signatures linked to PBMC preparation method (e.g., Trima apheresis), as well as ...
    Keywords scRNA-seq ; Sample multiplexing ; Sample preparation ; Alloreactivity ; PBMCs ; Biology (General) ; QH301-705.5
    Subject code 310
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Functional interpretation of single cell similarity maps

    David DeTomaso / Matthew G. Jones / Meena Subramaniam / Tal Ashuach / Chun J. Ye / Nir Yosef

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and ... ...

    Abstract The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and aids interpretation of cellular heterogeneity.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  4. Article ; Online: Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure

    Roy Oelen / Dylan H. de Vries / Harm Brugge / M. Grace Gordon / Martijn Vochteloo / single-cell eQTLGen consortium / BIOS Consortium / Chun J. Ye / Harm-Jan Westra / Lude Franke / Monique G. P. van der Wijst

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Not just differential gene expression but also differential gene regulation in immune cells account for individual differences in the immune response. Authors show here by single-cell RNA-sequencing of peripheral blood mononuclear cells from a large ... ...

    Abstract Not just differential gene expression but also differential gene regulation in immune cells account for individual differences in the immune response. Authors show here by single-cell RNA-sequencing of peripheral blood mononuclear cells from a large cohort of genetically diverse individuals that gene expression and regulatory changes in these cells depend on the context of and interactions between cell types, genetics, type of pathogen and time after exposure.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla

    Jhoanne L. Bautista / Nathan T. Cramer / Corey N. Miller / Jessica Chavez / David I. Berrios / Lauren E. Byrnes / Joe Germino / Vasilis Ntranos / Julie B. Sneddon / Trevor D. Burt / James M. Gardner / Chun J. Ye / Mark S. Anderson / Audrey V. Parent

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific ... ...

    Abstract The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.
    Keywords Science ; Q
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  6. Article ; Online: CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells

    Levi J. Rupp / Kathrin Schumann / Kole T. Roybal / Rachel E. Gate / Chun J. Ye / Wendell A. Lim / Alexander Marson

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 10

    Abstract: Abstract Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of ...

    Abstract Abstract Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Lineage dynamics of murine pancreatic development at single-cell resolution

    Lauren E. Byrnes / Daniel M. Wong / Meena Subramaniam / Nathaniel P. Meyer / Caroline L. Gilchrist / Sarah M. Knox / Aaron D. Tward / Chun J. Ye / Julie B. Sneddon

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying ...

    Abstract Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.
    Keywords Science ; Q
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Lineage dynamics of murine pancreatic development at single-cell resolution

    Lauren E. Byrnes / Daniel M. Wong / Meena Subramaniam / Nathaniel P. Meyer / Caroline L. Gilchrist / Sarah M. Knox / Aaron D. Tward / Chun J. Ye / Julie B. Sneddon

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying ...

    Abstract Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.
    Keywords Science ; Q
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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