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  1. Article ; Online: Protocol for inducing cellular ablation in the mouse atrioventricular conduction system.

    Wang, Lin / Dela Rosa, Jared Gabriel L / Munshi, Nikhil V

    STAR protocols

    2023  Volume 4, Issue 1, Page(s) 102145

    Abstract: Damage to the atrioventricular conduction system (AVCS), the main electrical connection between the atrial and ventricular chambers, can result in a variety of cardiac conduction disorders. Here, we provide a protocol for selective damage of the mouse ... ...

    Abstract Damage to the atrioventricular conduction system (AVCS), the main electrical connection between the atrial and ventricular chambers, can result in a variety of cardiac conduction disorders. Here, we provide a protocol for selective damage of the mouse AVCS to study its response during injury. We describe tamoxifen-induced cellular ablation, detection of AV block through electrocardiography, and quantification of histological and immunofluorescence markers to analyze the AVCS. This protocol can be used to study mechanisms associated with AVCS injury repair and regeneration. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).
    MeSH term(s) Animals ; Mice ; Atrioventricular Node/surgery ; Electrocardiography
    Language English
    Publishing date 2023-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102145
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  2. Article ; Online: CRISPR (Clustered Regularly Interspaced Palindromic Repeat)/Cas9 System: A Revolutionary Disease-Modifying Technology.

    Munshi, Nikhil V

    Circulation

    2016  Volume 134, Issue 11, Page(s) 777–779

    MeSH term(s) Animals ; CRISPR-Cas Systems ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/therapy ; Genetic Therapy/methods ; Humans
    Language English
    Publishing date 2016-09-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.116.024007
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  3. Article ; Online: Development of the Cardiac Conduction System.

    Bhattacharyya, Samadrita / Munshi, Nikhil V

    Cold Spring Harbor perspectives in biology

    2020  Volume 12, Issue 12

    Abstract: The cardiac conduction system initiates and propagates each heartbeat. Specialized conducting cells are a well-conserved phenomenon across vertebrate evolution, although mammalian and avian species harbor specific components unique to organisms with four- ...

    Abstract The cardiac conduction system initiates and propagates each heartbeat. Specialized conducting cells are a well-conserved phenomenon across vertebrate evolution, although mammalian and avian species harbor specific components unique to organisms with four-chamber hearts. Early histological studies in mammals provided evidence for a dominant pacemaker within the right atrium and clarified the existence of the specialized muscular axis responsible for atrioventricular conduction. Building on these seminal observations, contemporary genetic techniques in a multitude of model organisms has characterized the developmental ontogeny, gene regulatory networks, and functional importance of individual anatomical compartments within the cardiac conduction system. This review describes in detail the transcriptional and regulatory networks that act during cardiac conduction system development and homeostasis with a particular emphasis on networks implicated in human electrical variation by large genome-wide association studies. We conclude with a discussion of the clinical implications of these studies and describe some future directions.
    MeSH term(s) Animals ; Autonomic Nervous System/physiology ; Electrocardiography ; Gap Junctions/physiology ; Heart Conduction System/embryology ; Heart Conduction System/physiology ; Humans
    Language English
    Publishing date 2020-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a037408
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  4. Article ; Online: Resident Macrophages: Near and Dear to Your Heart.

    Munshi, Nikhil V

    Cell

    2016  Volume 169, Issue 3, Page(s) 376–377

    Abstract: In this issue of Cell, Hulsmans et al. identify a subset of macrophages residing within the cardiac conduction system, which orchestrates cardiac rhythm. Macrophages directly couple with cardiomyocytes, and their perturbation alters cardiac conduction, ... ...

    Abstract In this issue of Cell, Hulsmans et al. identify a subset of macrophages residing within the cardiac conduction system, which orchestrates cardiac rhythm. Macrophages directly couple with cardiomyocytes, and their perturbation alters cardiac conduction, suggesting that pharmacological manipulation of resident macrophages might represent a new strategy to combat cardiac arrhythmias.
    MeSH term(s) Arrhythmias, Cardiac ; Heart Conduction System ; Humans ; Macrophages ; Myocytes, Cardiac
    Language English
    Publishing date 2016-09-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.04.002
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  5. Article: Resident Macrophages: Near and Dear to Your Heart

    Munshi, Nikhil V

    Cell. 2017 Apr. 20, v. 169

    2017  

    Abstract: In this issue of Cell, Hulsmans et al. identify a subset of macrophages residing within the cardiac conduction system, which orchestrates cardiac rhythm. Macrophages directly couple with cardiomyocytes, and their perturbation alters cardiac conduction, ...

    Abstract In this issue of Cell, Hulsmans et al. identify a subset of macrophages residing within the cardiac conduction system, which orchestrates cardiac rhythm. Macrophages directly couple with cardiomyocytes, and their perturbation alters cardiac conduction, suggesting that pharmacological manipulation of resident macrophages might represent a new strategy to combat cardiac arrhythmias.
    Keywords arrhythmia ; cardiomyocytes ; macrophages
    Language English
    Dates of publication 2017-0420
    Size p. 376-377.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.04.002
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  6. Article ; Online: CHD-associated enhancers shape human cardiomyocyte lineage commitment.

    Armendariz, Daniel A / Goetsch, Sean C / Sundarrajan, Anjana / Sivakumar, Sushama / Wang, Yihan / Xie, Shiqi / Munshi, Nikhil V / Hon, Gary C

    eLife

    2023  Volume 12

    Abstract: Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many ... ...

    Abstract Enhancers orchestrate gene expression programs that drive multicellular development and lineage commitment. Thus, genetic variants at enhancers are thought to contribute to developmental diseases by altering cell fate commitment. However, while many variant-containing enhancers have been identified, studies to endogenously test the impact of these enhancers on lineage commitment have been lacking. We perform a single-cell CRISPRi screen to assess the endogenous roles of 25 enhancers and putative cardiac target genes implicated in genetic studies of congenital heart defects (CHDs). We identify 16 enhancers whose repression leads to deficient differentiation of human cardiomyocytes (CMs). A focused CRISPRi validation screen shows that repression of TBX5 enhancers delays the transcriptional switch from mid- to late-stage CM states. Endogenous genetic deletions of two TBX5 enhancers phenocopy epigenetic perturbations. Together, these results identify critical enhancers of cardiac development and suggest that misregulation of these enhancers could contribute to cardiac defects in human patients.
    MeSH term(s) Humans ; Myocytes, Cardiac/metabolism ; Regulatory Sequences, Nucleic Acid ; Cell Differentiation/genetics ; Heart Defects, Congenital/genetics
    Language English
    Publishing date 2023-04-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.86206
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  7. Article ; Online: Inducible cardiomyocyte injury within the atrioventricular conduction system uncovers latent regenerative capacity in mice.

    Wang, Lin / Bhakta, Minoti / Fernandez-Perez, Antonio / Munshi, Nikhil V

    The Journal of clinical investigation

    2021  Volume 131, Issue 19

    Abstract: The cardiac conduction system (CCS) ensures regular contractile function, and injury to any of its components can cause cardiac dysrhythmia. Although all cardiomyocytes (CMs) originate from common progenitors, the CCS is composed of biologically distinct ...

    Abstract The cardiac conduction system (CCS) ensures regular contractile function, and injury to any of its components can cause cardiac dysrhythmia. Although all cardiomyocytes (CMs) originate from common progenitors, the CCS is composed of biologically distinct cell types with unique functional and developmental characteristics. In contrast to ventricular cardiomyocytes, which continue to proliferate after birth, most CCS cells terminally exit the cell cycle during fetal development. Although the CCS should thus provide a poor substrate for postnatal injury repair, its regenerative capacity remains untested. Here, we describe a genetic system for ablating CMs that reside within the atrioventricular conduction system (AVCS). Adult mouse AVCS ablation resulted in regenerative failure characterized by persistent atrioventricular conduction defects and contractile dysfunction. In contrast, AVCS injury in neonatal mice led to recovery in a subset of these mice, thus providing evidence for CCS plasticity. Furthermore, CM proliferation did not appear to completely account for the observed functional recovery, suggesting that mechanisms regulating recovery from dysrhythmia are likely to be distinct from cardiac regeneration associated with ventricular injury. Taken together, we anticipate that our results will motivate further mechanistic studies of CCS plasticity and enable the exploration of rhythm restoration as an alternative therapeutic strategy.
    MeSH term(s) Animals ; Atrioventricular Node/injuries ; Atrioventricular Node/physiology ; Cell Plasticity/physiology ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/physiology ; Regeneration/physiology
    Language English
    Publishing date 2021-09-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI138637
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  8. Article ; Online: The Promise of Cardiac Regeneration by In Situ Lineage Conversion.

    Nam, Young-Jae / Munshi, Nikhil V

    Circulation

    2017  Volume 135, Issue 10, Page(s) 914–916

    MeSH term(s) Animals ; Cell Lineage ; Cellular Reprogramming ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Heart/physiology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Regeneration
    Language English
    Publishing date 2017-03-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.116.025830
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  9. Article ; Online: Accurate Classification of Cardiomyopathy Diagnosis by Chromatin Accessibility.

    Bhattacharyya, Samadrita / Duan, Jialei / Vela, Ryan J / Bhakta, Minoti / Bajona, Pietro / Mammen, Pradeep P A / Hon, Gary C / Munshi, Nikhil V

    Circulation

    2022  Volume 146, Issue 11, Page(s) 878–881

    MeSH term(s) Cardiomyopathies/diagnosis ; Cardiomyopathies/genetics ; Chromatin/genetics ; Humans ; Medical History Taking
    Chemical Substances Chromatin
    Language English
    Publishing date 2022-09-12
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.122.059659
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  10. Article ; Online: Even after SARS-CoV-2 booster, there is increased COVID-19 breakthrough infection in patients with plasma cell disorders.

    Fillmore, Nathanael R / La, Jennifer / Wu, Julie Tsu-Yu / Corrigan, June K / Branch-Elliman, Westyn / Monach, Paul / Brophy, Mary T / Do, Nhan V / Munshi, Nikhil C

    Blood advances

    2023  Volume 7, Issue 21, Page(s) 6767–6770

    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Breakthrough Infections ; Plasma Cells ; COVID-19 Vaccines
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2023-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023011063
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