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  1. Article: Multiplex generation and single cell analysis of structural variants in a mammalian genome.

    Pinglay, Sudarshan / Lalanne, Jean-Benoit / Daza, Riza M / Koeppel, Jonas / Li, Xiaoyi / Lee, David S / Shendure, Jay

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The functional consequences of structural variants (SVs) in mammalian genomes are challenging to study. This is due to several factors, including: 1) their numerical paucity relative to other forms of standing genetic variation such as single nucleotide ... ...

    Abstract The functional consequences of structural variants (SVs) in mammalian genomes are challenging to study. This is due to several factors, including: 1) their numerical paucity relative to other forms of standing genetic variation such as single nucleotide variants (SNVs) and short insertions or deletions (indels); 2) the fact that a single SV can involve and potentially impact the function of more than one gene and/or
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.22.576756
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pluripotent stem cell-derived model of the post-implantation human embryo.

    Weatherbee, Bailey A T / Gantner, Carlos W / Iwamoto-Stohl, Lisa K / Daza, Riza M / Hamazaki, Nobuhiko / Shendure, Jay / Zernicka-Goetz, Magdalena

    Nature

    2023  Volume 622, Issue 7983, Page(s) 584–593

    Abstract: The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important ...

    Abstract The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important tools for interrogating developmental events and tissue-tissue crosstalk during these stages
    MeSH term(s) Female ; Humans ; Pregnancy ; Bone Morphogenetic Proteins ; Cell Differentiation ; Embryo Implantation ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryoid Bodies/cytology ; Embryonic Development ; Germ Layers/cytology ; Germ Layers/embryology ; Human Embryonic Stem Cells/cytology ; Models, Biological ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Pluripotent Stem Cells/cytology
    Chemical Substances Bone Morphogenetic Proteins ; SOX17 protein, human ; Transcription Factors
    Language English
    Publishing date 2023-06-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06368-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Publisher Correction: Pluripotent stem cell-derived model of the post-implantation human embryo.

    Weatherbee, Bailey A T / Gantner, Carlos W / Iwamoto-Stohl, Lisa K / Daza, Riza M / Hamazaki, Nobuhiko / Shendure, Jay / Zernicka-Goetz, Magdalena

    Nature

    2023  Volume 621, Issue 7977, Page(s) E30

    Language English
    Publishing date 2023-08-17
    Publishing country England
    Document type Published Erratum
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06524-4
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  4. Article: Induction and

    Hamazaki, Nobuhiko / Yang, Wei / Kubo, Connor / Qiu, Chengxiang / Martin, Beth K / Garge, Riddhiman K / Regalado, Samuel G / Nichols, Eva / Lee, Choli / Daza, Riza M / Srivatsan, Sanjay / Shendure, Jay

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Embryonic organoids are emerging as powerful models for studying early mammalian development. For example, stem cell-derived 'gastruloids' form elongating structures containing all three germ ... ...

    Abstract Embryonic organoids are emerging as powerful models for studying early mammalian development. For example, stem cell-derived 'gastruloids' form elongating structures containing all three germ layers
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.10.579769
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  5. Article: Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements.

    Chardon, Florence M / McDiarmid, Troy A / Page, Nicholas F / Daza, Riza M / Martin, Beth / Domcke, Silvia / Regalado, Samuel G / Lalanne, Jean-Benoît / Calderon, Diego / Li, Xiaoyi / Starita, Lea M / Sanders, Stephan J / Ahituv, Nadav / Shendure, Jay

    bioRxiv : the preprint server for biology

    2024  

    Abstract: CRISPR-based gene activation (CRISPRa) is a promising therapeutic approach for gene therapy, upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines ...

    Abstract CRISPR-based gene activation (CRISPRa) is a promising therapeutic approach for gene therapy, upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive
    Language English
    Publishing date 2024-04-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.28.534017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.

    Abadie, Kathleen / Clark, Elisa C / Valanparambil, Rajesh M / Ukogu, Obinna / Yang, Wei / Daza, Riza M / Ng, Kenneth K H / Fathima, Jumana / Wang, Allan L / Lee, Judong / Nasti, Tahseen H / Bhandoola, Avinash / Nourmohammad, Armita / Ahmed, Rafi / Shendure, Jay / Cao, Junyue / Kueh, Hao Yuan

    Immunity

    2024  Volume 57, Issue 2, Page(s) 271–286.e13

    Abstract: The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. ... ...

    Abstract The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8
    MeSH term(s) CD8-Positive T-Lymphocytes ; Memory T Cells ; Epigenesis, Genetic ; Clone Cells ; Immunologic Memory ; Cell Differentiation
    Language English
    Publishing date 2024-01-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2023.12.006
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  7. Article ; Online: Chromatin context-dependent regulation and epigenetic manipulation of prime editing.

    Li, Xiaoyi / Chen, Wei / Martin, Beth K / Calderon, Diego / Lee, Choli / Choi, Junhong / Chardon, Florence M / McDiarmid, Troy A / Daza, Riza M / Kim, Haedong / Lalanne, Jean-Benoît / Nathans, Jenny F / Lee, David S / Shendure, Jay

    Cell

    2024  Volume 187, Issue 10, Page(s) 2411–2427.e25

    Abstract: We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover ... ...

    Abstract We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target site and edit. Position effects on prime editing efficiency are well predicted by chromatin marks, e.g., positively by H3K79me2 and negatively by H3K9me3. Next, we developed a multiplex perturbational framework to assess the interaction of trans-acting factors with the cis-chromatin environment on editing outcomes. Applying this framework to DNA repair factors, we identify HLTF as a context-dependent repressor of prime editing. Finally, several lines of evidence suggest that active transcriptional elongation enhances prime editing. Consistent with this, we show we can robustly decrease or increase the efficiency of prime editing by preceding it with CRISPR-mediated silencing or activation, respectively.
    MeSH term(s) Chromatin/metabolism ; Chromatin/genetics ; Gene Editing/methods ; Humans ; Epigenesis, Genetic ; CRISPR-Cas Systems/genetics ; Histones/metabolism ; HEK293 Cells ; Transcription Factors/metabolism
    Chemical Substances Chromatin ; Histones ; Transcription Factors
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2024.03.020
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  8. Article ; Online: High-capacity sample multiplexing for single cell chromatin accessibility profiling.

    Booth, Gregory T / Daza, Riza M / Srivatsan, Sanjay R / McFaline-Figueroa, José L / Gladden, Rula Green / Mullen, Andrew C / Furlan, Scott N / Shendure, Jay / Trapnell, Cole

    BMC genomics

    2023  Volume 24, Issue 1, Page(s) 737

    Abstract: Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel ... ...

    Abstract Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.
    MeSH term(s) Chromatin/genetics ; DNA/genetics ; Chromatin Immunoprecipitation Sequencing ; Sequence Analysis, DNA/methods ; Epigenomics/methods
    Chemical Substances Chromatin ; DNA (9007-49-2)
    Language English
    Publishing date 2023-12-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-023-09832-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: High-Capacity Sample Multiplexing for Single Cell Chromatin Accessibility Profiling.

    Booth, Gregory T / Daza, Riza M / Srivatsan, Sanjay R / McFaline-Figueroa, José L / Gladden, Rula Green / Furlan, Scott N / Shendure, Jay / Trapnell, Cole

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel ... ...

    Abstract Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.05.531201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Comprehensive characterization of tissue-specific chromatin accessibility in L2

    Durham, Timothy J / Daza, Riza M / Gevirtzman, Louis / Cusanovich, Darren A / Bolonduro, Olubusayo / Noble, William Stafford / Shendure, Jay / Waterston, Robert H

    Genome research

    2021  Volume 31, Issue 10, Page(s) 1952–1969

    Abstract: Recently developed single-cell technologies allow researchers to characterize cell states at ever greater resolution and scale. ...

    Abstract Recently developed single-cell technologies allow researchers to characterize cell states at ever greater resolution and scale.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Chromatin/genetics ; Chromatin Immunoprecipitation Sequencing ; DNA/genetics ; Gene Expression Regulation
    Chemical Substances Chromatin ; DNA (9007-49-2)
    Language English
    Publishing date 2021-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.271791.120
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