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  1. Article ; Online: Single-cell transcriptome sequencing

    Serena Liu / Cole Trapnell

    F1000Research, Vol

    recent advances and remaining challenges [version 1; referees: 2 approved]

    2016  Volume 5

    Abstract: Single-cell RNA-sequencing methods are now robust and economically practical and are becoming a powerful tool for high-throughput, high-resolution transcriptomic analysis of cell states and dynamics. Single-cell approaches circumvent the averaging ... ...

    Abstract Single-cell RNA-sequencing methods are now robust and economically practical and are becoming a powerful tool for high-throughput, high-resolution transcriptomic analysis of cell states and dynamics. Single-cell approaches circumvent the averaging artifacts associated with traditional bulk population data, yielding new insights into the cellular diversity underlying superficially homogeneous populations. Thus far, single-cell RNA-sequencing has already shown great effectiveness in unraveling complex cell populations, reconstructing developmental trajectories, and modeling transcriptional dynamics. Ongoing technical improvements to single-cell RNA-sequencing throughput and sensitivity, the development of more sophisticated analytical frameworks for single-cell data, and an increasing array of complementary single-cell assays all promise to expand the usefulness and potential applications of single-cell transcriptomic profiling.
    Keywords Bioinformatics ; Cell Growth & Division ; Control of Gene Expression ; Developmental Molecular Mechanisms ; Genomics ; Neurodevelopment ; Nuclear Structure & Function ; Stem Cells & Regeneration ; Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2016-02-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Extreme heterogeneity of influenza virus infection in single cells

    Alistair B Russell / Cole Trapnell / Jesse D Bloom

    eLife, Vol

    2018  Volume 7

    Abstract: Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus ... ...

    Abstract Viral infection can dramatically alter a cell’s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription – viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.
    Keywords single-cell RNAseq ; influenza virus ; defective particle ; interferons ; stochasiticity ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2018-02-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Nuclear oligo hashing improves differential analysis of single-cell RNA-seq

    Hyeon-Jin Kim / Greg Booth / Lauren Saunders / Sanjay Srivatsan / José L. McFaline-Figueroa / Cole Trapnell

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

    2022  Volume 12

    Abstract: Using spike-in controls with current single cell RNA-seq platforms remains a challenge. Here, the authors use a mixture of short, unmodified DNA oligos as a normalization standard for sci-RNAseq to improve the detection of global transcriptome changes. ...

    Abstract Using spike-in controls with current single cell RNA-seq platforms remains a challenge. Here, the authors use a mixture of short, unmodified DNA oligos as a normalization standard for sci-RNAseq to improve the detection of global transcriptome changes.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Transcriptomic profiling of tissue environments critical for post-embryonic patterning and morphogenesis of zebrafish skin

    Andrew J Aman / Lauren M Saunders / August A Carr / Sanjay Srivatasan / Colten Eberhard / Blake Carrington / Dawn Watkins-Chow / William J Pavan / Cole Trapnell / David M Parichy

    eLife, Vol

    2023  Volume 12

    Abstract: Pigment patterns and skin appendages are prominent features of vertebrate skin. In zebrafish, regularly patterned pigment stripes and an array of calcified scales form simultaneously in the skin during post-embryonic development. Understanding the ... ...

    Abstract Pigment patterns and skin appendages are prominent features of vertebrate skin. In zebrafish, regularly patterned pigment stripes and an array of calcified scales form simultaneously in the skin during post-embryonic development. Understanding the mechanisms that regulate stripe patterning and scale morphogenesis may lead to the discovery of fundamental mechanisms that govern the development of animal form. To learn about cell types and signaling interactions that govern skin patterning and morphogenesis, we generated and analyzed single-cell transcriptomes of skin from wild-type fish as well as fish having genetic or transgenically induced defects in squamation or pigmentation. These data reveal a previously undescribed population of epidermal cells that express transcripts encoding enamel matrix proteins, suggest hormonal control of epithelial–mesenchymal signaling, clarify the signaling network that governs scale papillae development, and identify a critical role for the hypodermis in supporting pigment cell development. Additionally, these comprehensive single-cell transcriptomic data representing skin phenotypes of biomedical relevance should provide a useful resource for accelerating the discovery of mechanisms that govern skin development and homeostasis.
    Keywords squamation ; skin ; pigment ; morphogenesis ; adult form ; differentiation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Trajectory analysis quantifies transcriptional plasticity during macrophage polarization

    Serena X. Liu / Heather H. Gustafson / Dana L. Jackson / Suzie H. Pun / Cole Trapnell

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

    2020  Volume 9

    Abstract: Abstract In recent years, macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; however, it remains unclear whether macrophages retain any persistent memory of past polarization states which may then impact their ... ...

    Abstract Abstract In recent years, macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; however, it remains unclear whether macrophages retain any persistent memory of past polarization states which may then impact their future repolarization to new states. Here, we perform deep transcriptomic profiling at high temporal resolution as macrophages are polarized with cytokines that drive them into “M1” and “M2” molecular states. We find through trajectory analysis of their global transcriptomic profiles that macrophages which are first polarized to M1 or M2 and then subsequently repolarized demonstrate little to no memory of their polarization history. We observe complete repolarization both from M1 to M2 and vice versa, and we find that macrophage transcriptional phenotypes are defined by the current cell microenvironment, rather than an amalgamation of past and present states.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Dimensionality reduction by UMAP to visualize physical and genetic interactions

    Michael W. Dorrity / Lauren M. Saunders / Christine Queitsch / Stanley Fields / Cole Trapnell

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

    2020  Volume 6

    Abstract: Dimensionality reduction is often used to visualize expression profiling data in order to find relationships among cells. Here, the authors use Uniform Manifold Approximation and Projection (UMAP) on published expression data of gene deletions of S. ... ...

    Abstract Dimensionality reduction is often used to visualize expression profiling data in order to find relationships among cells. Here, the authors use Uniform Manifold Approximation and Projection (UMAP) on published expression data of gene deletions of S. cerevisiae to find novel protein interactions.
    Keywords 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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  7. Article ; Online: Dimensionality reduction by UMAP to visualize physical and genetic interactions

    Michael W. Dorrity / Lauren M. Saunders / Christine Queitsch / Stanley Fields / Cole Trapnell

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

    2020  Volume 6

    Abstract: Dimensionality reduction is often used to visualize expression profiling data in order to find relationships among cells. Here, the authors use Uniform Manifold Approximation and Projection (UMAP) on published expression data of gene deletions of S. ... ...

    Abstract Dimensionality reduction is often used to visualize expression profiling data in order to find relationships among cells. Here, the authors use Uniform Manifold Approximation and Projection (UMAP) on published expression data of gene deletions of S. cerevisiae to find novel protein interactions.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Airway epithelial interferon response to SARS-CoV-2 is inferior to rhinovirus and heterologous rhinovirus infection suppresses SARS-CoV-2 replication

    Elizabeth R. Vanderwall / Kaitlyn A. Barrow / Lucille M. Rich / David F. Read / Cole Trapnell / Oghenemega Okoloko / Steven F. Ziegler / Teal S. Hallstrand / Maria P. White / Jason S. Debley

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Abstract Common alphacoronaviruses and human rhinoviruses (HRV) induce type I and III interferon (IFN) responses important to limiting viral replication in the airway epithelium. In contrast, highly pathogenic betacoronaviruses including SARS-CoV-2 may ... ...

    Abstract Abstract Common alphacoronaviruses and human rhinoviruses (HRV) induce type I and III interferon (IFN) responses important to limiting viral replication in the airway epithelium. In contrast, highly pathogenic betacoronaviruses including SARS-CoV-2 may evade or antagonize RNA-induced IFN I/III responses. In airway epithelial cells (AECs) from children and older adults we compared IFN I/III responses to SARS-CoV-2 and HRV-16, and assessed whether pre-infection with HRV-16, or pretreatment with recombinant IFN-β or IFN-λ, modified SARS-CoV-2 replication. Bronchial AECs from children (ages 6–18 years) and older adults (ages 60–75 years) were differentiated ex vivo to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 or HRV-16, and RNA and protein was harvested from cell lysates 96 h. following infection and supernatant was collected 48 and 96 h. following infection. In additional experiments cultures were pre-infected with HRV-16, or pre-treated with recombinant IFN-β1 or IFN-λ2 before SARS-CoV-2 infection. In a subset of experiments a range of infectious concentrations of HRV-16, SARS-CoV-2 WA-01, SARS-CoV-2 Delta variant, and SARS-CoV-2 Omicron variant were studied. Despite significant between-donor heterogeneity SARS-CoV-2 replicated 100 times more efficiently than HRV-16. IFNB1, INFL2, and CXCL10 gene expression and protein production following HRV-16 infection was significantly greater than following SARS-CoV-2. IFN gene expression and protein production were inversely correlated with SARS-CoV-2 replication. Treatment of cultures with recombinant IFNβ1 or IFNλ2, or pre-infection of cultures with HRV-16, markedly reduced SARS-CoV-2 replication. In addition to marked between-donor heterogeneity in IFN responses and viral replication, SARS-CoV-2 (WA-01, Delta, and Omicron variants) elicits a less robust IFN response in primary AEC cultures than does rhinovirus, and heterologous rhinovirus infection, or treatment with recombinant IFN-β1 or IFN-λ2, ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics

    Brandon Hadland / Barbara Varnum-Finney / Stacey Dozono / Tessa Dignum / Cynthia Nourigat-McKay / Adam M. Heck / Takashi Ishida / Dana L. Jackson / Tomer Itkin / Jason M. Butler / Shahin Rafii / Cole Trapnell / Irwin D. Bernstein

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

    2022  Volume 17

    Abstract: Here, the authors use single cell RNA-sequencing to generate an atlas of signaling interactions regulating embryonic hematopoietic stem cell (HSC) development and apply this knowledge to engineer a niche sufficient to support HSC maturation in vitro. ...

    Abstract Here, the authors use single cell RNA-sequencing to generate an atlas of signaling interactions regulating embryonic hematopoietic stem cell (HSC) development and apply this knowledge to engineer a niche sufficient to support HSC maturation in vitro.
    Keywords Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation

    Giancarlo Bonora / Vijay Ramani / Ritambhara Singh / He Fang / Dana L. Jackson / Sanjay Srivatsan / Ruolan Qiu / Choli Lee / Cole Trapnell / Jay Shendure / Zhijun Duan / Xinxian Deng / William S. Noble / Christine M. Disteche

    Genome Biology, Vol 22, Iss 1, Pp 1-

    2021  Volume 36

    Abstract: Abstract Background Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation ... ...

    Abstract Abstract Background Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data from these three modalities obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C. Results Allele-specific contact decay profiles obtained by single-cell Hi-C clearly show that the inactive X chromosome has a unique profile in differentiated cells that have undergone X inactivation. Loss of this inactive X-specific structure at mitosis is followed by its reappearance during the cell cycle, suggesting a “bookmark” mechanism. Differentiation of embryonic stem cells to follow the onset of X inactivation is associated with changes in contact decay profiles that occur in parallel on both the X chromosomes and autosomes. Single-cell RNA-seq and ATAC-seq show evidence of a delay in female versus male cells, due to the presence of two active X chromosomes at early stages of differentiation. The onset of the inactive X-specific structure in single cells occurs later than gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Single-cell Hi-C highlights evidence of discrete changes in nuclear structure characterized by the acquisition of very long-range contacts throughout the nucleus. Novel computational approaches allow for the effective alignment of single-cell gene expression, chromatin accessibility, and 3D chromosome structure. Conclusions Based on trajectory analyses, three distinct nuclear structure states are detected reflecting discrete and profound simultaneous changes not only to the structure of the X chromosomes, but also to that of autosomes during differentiation. Our study reveals that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.
    Keywords Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Subject code 571
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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