Polyploidy and nuclear phenotype characteristics of cardiomyocytes from diabetic adult and normoglycemic aged mice

Silva, Isabela S.; Ghiraldini, Flávia Gerelli; Veronezi, Giovana M. B.; Mello, Maria Luiza S.

doi:10.1016/j.acthis.2017.12.003

Cited by 14 publications

(16 citation statements)

References 39 publications

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“…Higher frequency of diploid cardiomyocytes correlated with better physiologic recovery from myocardial infarction in a survey of multiple murine strains 16 . Diabetic stress also influenced the ploidy level of cardiomyocytes 85 . Although increased numbers of CICs in response to infarction are evident in mammalian models, only one prior publication examined ploidy of the non-myocyte population and concluded that human CICs are diploid 86 , consistent with our finding that human cCICs are diploid in situ and upon isolation and expansion.…”

Section: Discussionmentioning

confidence: 99%

Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals

et al. 2019

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Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials.

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Section: Discussionmentioning

confidence: 99%

Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals

et al. 2019

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“…Higher frequency of diploid cardiomyocytes correlated with better physiologic recovery to myocardial infarction in a survey of multiple murine strains 16 . Diabetic stress also influenced the ploidy level of cardiomyocytes 84 . Although increased numbers of CICs in response to infarction is evident in mammalian models, only one prior publication examined ploidy of the non-myocyte population and concluded that human CICs are diploid 85 , consistent with our finding that human ckit+ CICs are diploid in situ and upon isolation and expansion.…”

Section: Discussionmentioning

confidence: 99%

Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals

Broughton

Khieu

Nguyen

et al. 2019

Preprint

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Ploidy for cardiomyocytes is well described but remains obscure in cardiac interstitial cells (CICs). Ploidy of c-kit+CICs (cCICs) were assessed using a combination of confocal, karyotypic, and flow cytometric assessments coupled with molecular and bioinformatic analyses. Fundamental differences were found between cultured rodent (rat, mouse) cCICs possessing mononuclear tetraploid (4n) content versus large mammal (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in cCICs from human and a mixture of diploid and tetraploid nuclei in mouse. Molecular assessment of the p53 signaling pathway provides a plausible explanation for escape from replicative senescence in rodent but not human cCICs. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse cCICs, alluding to functional divergences. Collectively, these data reveal fundamental species-specific biological differences in cCICs that could account for challenges in extrapolation of myocardial preclinical studies from rodent to large animal models.

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“…Transcriptome activity changes due to WGDs may be mediated by epigenetic chromatin modifications associated with DNA methylation; modification of histones and nonhistone chromatin regulators, such as HNMGB1 and HMGB2; and changes in microRNA expression [121][122][123][124][125]. An association of chromatin decompaction with polyploidy was observed in studies with hepatocytes and cardiomyocytes [121,126,127]. Polyploidy may be additionally accompanied by changes in the balance of antagonistic activities of the Trithorax and Polycomb histone methyltransferase complexes, which regulate histone methylation in CpG-rich regions and modulate expression of many gene modules, as was observed in cardiomyocytes, dedicual cells, hepatocytes, cultured carcinoma cells, and plant cells [104,121,128,129].…”

Section: Common Effects Of Whole-genomementioning

confidence: 98%

Whole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves

Anatskaya

Vinogradov

2021

Mol Biol

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Whole-genome duplication (WGD), or polyploidy, increases the amount of genetic information in the cell. WGDs of whole organisms are found in all branches of eukaryotes and act as a driving force of speciation, complication, and adaptations. Somatic-cell WGDs are observed in all types of tissues and can result from normal or altered ontogenetic programs, regeneration, pathological conditions, aging, malignancy, and metastasis. Despite the versatility of WGDs, their functional significance, general properties, and causes of their higher adaptive potential are unclear. Comparisons of whole-transcriptome data and information from various fields of molecular biology, genomics, and molecular medicine showed several common features for polyploidy of organisms and somatic and cancer cells, making it possible to understand what WGD properties lead to the emergence of an adaptive phenotype. The adaptation potential of WGDs may be associated with an increase in the complexity of the regulation of networks and signaling systems; a higher resistance to stress; and activation of ancient evolutionary programs of unicellularity and pathways of morphogenesis, survival, and life extension. A balance between the cell and organismal levels in controlling gene regulation may shift in stress towards the priority of cell survival, and the shift can lead to cardiovascular diseases and carcinogenesis. The presented information helps to understand how polyploidy creates new phenotypes and why it acts as a driving force of evolution and an important regulator of biological processes in somatic cells during ontogeny, pathogenesis, regeneration, and transformation.

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Polyploidy and nuclear phenotype characteristics of cardiomyocytes from diabetic adult and normoglycemic aged mice

Cited by 14 publications

References 39 publications

Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals

Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals

Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals

Whole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves

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