Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies

Windmueller, Rebecca; Leach, John P.; Babu, Apoorva; Zhou, Shanshan; Morley, Michael; Wakabayashi, Aoi; Petrenko, Nataliya; Viatour, Patrick; Morrisey, Edward E.

doi:10.1016/j.celrep.2020.02.034

Cited by 55 publications

(58 citation statements)

References 54 publications

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“…Ect2 generates guanosine triphosphate during contractile ring assembly & cytokinesis initiation; its loss of function in ZF promotes CM polyploidization (González-Rosa et al 2018 ). Likewise, Ect2 loss in neonatal CMs enhances developmental binucleation of the myocardium and downregulates proliferative pathways like E2f target genes,(Windmueller et al 2020 ) whereas increasing neonatal Ect2 activity via chemical inhibition of β-adrenergic signaling conversely increases both total CM number and the fraction of mononuclear CMs (Liu et al 2019 ). This reduced CM ploidy and increased CM endowment phenotype persists into adulthood, enabling superior functional recovery of the heart after myocardial infarction (Liu et al 2019 ).…”

Section: New Players: Cellular Participators and Molecular Regulatorsmentioning

confidence: 99%

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Cutie

Huang

2021

Cell Regen

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Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures, and as members of certain species developmentally progress towards their adult forms. While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults, neonates of these same species can fully regenerate heart structure and function after injury – as can adult lower vertebrates like many teleost fish and urodele amphibians. Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally: an oxygen-rich environment, vertebrate thermogenesis, a complex adaptive immune system, and cancer risk trade-offs. In this review, we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.

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Section: New Players: Cellular Participators and Molecular Regulatorsmentioning

confidence: 99%

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Cutie

Huang

2021

Cell Regen

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“…However, nuclear extraction disrupts the cellular integrity and thus does not distinguish nuclei from mononucleated cardiomyocytes from those of binucleated cardiomyocytes. To correlate the subtypes to nucleation, other supporting information such as visualization of the subsets via immunostaining or in-situ hybridization or direct comparison of isolated mononucleated and binucleated cardiomyocytes, as recently reported ( Windmueller et al. 2020 ), are needed.…”

Section: Limitationsmentioning

confidence: 99%

Protocol for Single-Nucleus Transcriptomics of Diploid and Tetraploid Cardiomyocytes in Murine Hearts

Cui

Olson

2020

STAR Protocols

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Summary Murine cardiomyocytes undergo proliferation, multinucleation, and polyploidization during the first 3 weeks of postnatal life, resulting in a mixture of diploid and tetraploid cardiomyocytes in the heart. Understanding the molecular differences between diploid and tetraploid cardiomyocytes from these processes has been limited due to lack of unique markers and their heterogenous origins. Here, we apply single-nucleus RNA-sequencing to fluorescence-activated cell sorting-selected diploid and tetraploid cardiomyocytes to characterize their heterogeneity and molecular distinctions. For complete details on the use and execution of this protocol, please refer to Cui et al. (2020)

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“…Cardiomyocyte ploidy analyses were done with modification. 21 Isolated ventricular cardiomyocytes were enriched by centrifugation at 3000 RPM for 1 minute and resuspended in PBS supplemented with 1% goat serum. DAPI was added to the cell suspension (1:10,000 dilution) 3 mins prior to FACS.…”

Section: Ploidy Measurementmentioning

confidence: 99%

Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction

Peng

Shindo

Donahue

et al. 2020

Preprint

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Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and function. In this study, we characterized cardiac structure, anatomy, and in vivo function, as well as cardiomyocyte characteristics in Acomys compared to the most commonly used cardiac mouse model, the C57BL6 mouse strain (Mus). Our results demonstrate comparable cardiac anatomy, structure and function between the two rodent species, but reveal significant differences in their cardiomyocyte characteristics. These findings establish Acomys as a new mammalian model for cardiac research.

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Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies

Cited by 55 publications

References 54 publications

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Vertebrate cardiac regeneration: evolutionary and developmental perspectives

Protocol for Single-Nucleus Transcriptomics of Diploid and Tetraploid Cardiomyocytes in Murine Hearts

Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction

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