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Mono- and multi-nucleated ventricular cardiomyocytes constitute a transcriptionally homogenous cell population

Yekelchyk, Michail ; Guenther, Stefan ; Preussner, Jens ; Braun, Thomas

Basic research in cardiology, 2019-09, Vol.114 (5), p.36-13, Article 36 [Periódico revisado por pares]

Berlin/Heidelberg: Springer Berlin Heidelberg

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  • Título:
    Mono- and multi-nucleated ventricular cardiomyocytes constitute a transcriptionally homogenous cell population
  • Autor: Yekelchyk, Michail ; Guenther, Stefan ; Preussner, Jens ; Braun, Thomas
  • Assuntos: Animals ; Aorta ; Blood vessels ; Cardiology ; Cardiomegaly - pathology ; Cardiomyocytes ; Correlation analysis ; Gene sequencing ; Heart ; Heart Ventricles - cytology ; Heterogeneity ; Homogeneity ; Hypertrophy ; Hypoxia ; Image quality ; Immunofluorescence ; Male ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac - cytology ; Original Contribution ; Quality control ; Ribonucleic acid ; RNA ; Signatures ; Transcription ; Transcriptome ; Transcriptomes ; Ventricle
  • É parte de: Basic research in cardiology, 2019-09, Vol.114 (5), p.36-13, Article 36
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
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  • Descrição: Individual adult ventricular cardiomyocytes are either mono- or multi-nucleated and undergo morphological changes during cardiac hypertrophy. However, corresponding transcriptional signatures, reflecting potentially different functions or the ability for cell-cycle entry, are not known. The aim of this study was to determine the transcriptional profile of mono- and multi-nucleated adult cardiomyocytes by single-cell RNA-sequencing (scRNA-seq) and to investigate heterogeneity among cardiomyocytes under baseline conditions and in pressure-induced cardiac hypertrophy. We developed an array-based approach for scRNA-seq of rod-shaped multi-nucleated cardiomyocytes from both healthy and hypertrophic hearts. Single-cell transcriptomes of mono- or multi-nucleated cardiomyocytes were highly similar, although a certain degree of variation was noted across both populations. Non-image-based quality control allowing inclusion of damaged cardiomyocytes generated artificial cell clusters demonstrating the need for strict exclusion criteria. In contrast, cardiomyocytes isolated from hypertrophic heart after transverse aortic constriction showed heterogeneous transcriptional signatures, characteristic for hypoxia-induced responses. Immunofluorescence analysis revealed an inverse correlation between HIF1α + cells and CD31-stained vessels, suggesting that imbalanced vascular growth in the hypertrophied heart induces cellular heterogeneity. Our study demonstrates that individual mono- and multi-nucleated cardiomyocytes express nearly identical sets of genes. Homogeneity among cardiomyocytes was lost after induction of hypertrophy due to differential HIF1α-dependent responses most likely caused by none-homogenous vessel growth.
  • Editor: Berlin/Heidelberg: Springer Berlin Heidelberg
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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