The Role of TGF—β Signaling in Cardiomyocyte Proliferation

Sorensen, Daniel W.; Berlo, Jop H. van

doi:10.1007/s11897-020-00470-2

Cited by 28 publications

(25 citation statements)

References 78 publications

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“…Other agents involved in the interactions included BMP, LRP1 (low density lipoprotein receptor) and TNFR. BMP is a member of the TGF-beta superfamily and, along with NOTCH signaling, regulates CM proliferation (D’Amato et al, 2016; Sorensen and van Berlo, 2020). LRP1 affects cardiomyocyte lipid uptake, while TNFR activation may be involved in apoptosis, and has been described as recruiting cardiac progenitor cells (Allukian et al, 2013) and stimulating OFT CMs.…”

Section: Resultsmentioning

confidence: 99%

High cardiomyocyte diversity in human early prenatal heart development

Sylvén

Wärdell

Månsson‐Broberg

et al. 2022

Preprint

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Cardiomyocytes play key roles during cardiogenesis, but have poorly understood features, especially in prenatal stages. Thus, we have characterized human prenatal cardiomyocytes, 6.5–7 weeks post-conception, in detail by integrating single–cell RNA sequencing, spatial transcriptomics, and ligand–receptor interaction information. Using a computational workflow developed to dissect cell type heterogeneity, localize cell types, and explore their molecular interactions, we identified eight types of developing cardiomyocyte, more than double compared to the ones identified in the Human Developmental Cell Atlas. These have high variability in cell cycle activity, mitochondrial content, and connexin gene expression, and are differentially distributed in the ventricles, including outflow tract, and atria, including sinoatrial node. Moreover, cardiomyocyte ligand–receptor crosstalk is mainly with non–cardiomyocyte cell types, encompassing cardiogenesis-related pathways. Thus, early prenatal human cardiomyocytes are highly heterogeneous and develop unique location–dependent properties, with complex ligand–receptor crosstalk. Further elucidation of their developmental dynamics may give rise to new therapies.

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Section: Resultsmentioning

confidence: 99%

High cardiomyocyte diversity in human early prenatal heart development

Sylvén

Wärdell

Månsson‐Broberg

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…TGFβ1, TGFβ2, and TGFβ3, pleiotropic factors belonging to the transforming growth factor beta (TGFβ) superfamily, have emerged as crucial mediators of multiple cellular responses in the infarcted myocardium, including cardiac reparative, inflammatory, angiogenic, and fibrotic responses [reviewed by Frangogiannis (117), Hanna and Frangogiannis (118) and Sorensen and colleagues (119)]. The inhibition of TGFβ receptor 1 (TGFBR1) activity by SB-431542 was reported to reduce the number of proliferating cardiomyocytes in zebrafish embryos (120).…”

Section: Growth Factors and Cytokinesmentioning

confidence: 99%

Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

Bongiovanni

Sacchi

Pra

et al. 2021

Front. Cardiovasc. Med.

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Despite considerable efforts carried out to develop stem/progenitor cell-based technologies aiming at replacing and restoring the cardiac tissue following severe damages, thus far no strategies based on adult stem cell transplantation have been demonstrated to efficiently generate new cardiac muscle cells. Intriguingly, dedifferentiation, and proliferation of pre-existing cardiomyocytes and not stem cell differentiation represent the preponderant cellular mechanism by which lower vertebrates spontaneously regenerate the injured heart. Mammals can also regenerate their heart up to the early neonatal period, even in this case by activating the proliferation of endogenous cardiomyocytes. However, the mammalian cardiac regenerative potential is dramatically reduced soon after birth, when most cardiomyocytes exit from the cell cycle, undergo further maturation, and continue to grow in size. Although a slow rate of cardiomyocyte turnover has also been documented in adult mammals, both in mice and humans, this is not enough to sustain a robust regenerative process. Nevertheless, these remarkable findings opened the door to a branch of novel regenerative approaches aiming at reactivating the endogenous cardiac regenerative potential by triggering a partial dedifferentiation process and cell cycle re-entry in endogenous cardiomyocytes. Several adaptations from intrauterine to extrauterine life starting at birth and continuing in the immediate neonatal period concur to the loss of the mammalian cardiac regenerative ability. A wide range of systemic and microenvironmental factors or cell-intrinsic molecular players proved to regulate cardiomyocyte proliferation and their manipulation has been explored as a therapeutic strategy to boost cardiac function after injuries. We here review the scientific knowledge gained thus far in this novel and flourishing field of research, elucidating the key biological and molecular mechanisms whose modulation may represent a viable approach for regenerating the human damaged myocardium.

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“…In addition, the analysis indicated that some m 6 A differential lncRNAs were also enriched in 'insulin-like growth factor receptor' and 'response to angiotensin', which are participating in cardiac hypertrophy [36,44]. m 6 A differential lncRNAs enriched in myocardial regeneration-related pathways, such as 'TGF-beta signaling pathway' is well documented [62]. All the above indicates that m 6 A differential lncRNAs may play an important role in the heart normal or dysfunction development.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine modulates long non-coding RNA in the developing mouse heart

Shen

Liu

et al. 2022

Cell Death Discov.

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Long non-coding RNAs (lncRNAs) were reported to potentially play a regulatory role in the process of myocardial regeneration in the neonatal mouse. N6-methyladenosine (m6A) modification may play a key role in myocardial regeneration in mice and regulates a variety of biological processes through affecting the stability of lncRNAs. However, the map of m6A modification of lncRNAs in mouse cardiac development still remains unknown. We aimed to investigate the differences in the m6A status of lncRNAs during mouse cardiac development and reveal a potential role of m6A modification modulating lncRNAs in cardiac development and myocardial regeneration during cardiac development in mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) of the heart tissue in C57BL/6 J mice at postnatal day 1 (P1), P7 and P28 were performed to produce stagewise cardiac lncRNA m6A-methylomes in a parallel timeframe with the established loss of an intrinsic cardiac regeneration capacity and early postnatal development. There were significant differences in the distribution and abundance of m6A modifications in lncRNAs in the P7 vs P1 mice. In addition, the functional role of m6A in regulating lncRNA levels was established for selected transcripts with METTL3 silencing in neonatal cardiomyocytes in vitro. Based on our MeRIP-qPCR experiment data, both lncGm15328 and lncRNA Zfp597, that were not previously associated with cardiac regeneration, were found to be the most differently methylated at P1-P7. These two lncRNAs sponged several miRNAs which further regulated multiple mRNAs, including some of which have previously been linked with cardiac regeneration ability. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that differential m6A modifications were more enriched in functions and cellular signalling pathways related to cardiomyocyte proliferation. Our data suggested that the m6A modification on lncRNAs may play an important role in the regeneration of myocardium and cardiac development.

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The Role of TGF—β Signaling in Cardiomyocyte Proliferation

Cited by 28 publications

References 78 publications

High cardiomyocyte diversity in human early prenatal heart development

High cardiomyocyte diversity in human early prenatal heart development

Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes

N6-methyladenosine modulates long non-coding RNA in the developing mouse heart

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