Pub Date : 2025-09-17DOI: 10.1016/j.yjmcc.2025.09.002
Federica Diofano , Chidinma Amadi , Larissa Hartmann , Bernd M. Gahr , Karolina Weinmann-Emhardt , Wolfgang Rottbauer , Steffen Just
The SMYD family comprises a distinct class of lysine methyltransferases (KMTases) that methylate both histone and non-histone proteins. Among its five members (SMYD1–5), SMYD1 has been identified as a cardiac and skeletal muscle-specific KMTase that interacts with Myosin, in coordination with Unc45b and Hsp90a, to regulate thick filament assembly. However, the precise mechanism by which SMYD1 orchestrates Myosin assembly remains largely unknown.
Here, we demonstrate that SMYD1 physically associates with the N-terminal region of several myosin heavy chain (MyHC) isoforms and specifically catalyzes the mono-methylation of MyHC at lysine 35 (K35). Methylated MyHC is correctly incorporated into sarcomeres, whereas unmethylated MyHC in Smyd1-deficient zebrafish undergoes degradation via the ubiquitin-proteasome system (UPS), leading to defective thick filament assembly. Although UPS inhibition with MG132 restores Myosin levels in Smyd1-deficient zebrafish embryos, proper thick filament assembly remains impaired due to the absence of K35 MyHC mono-methylation.
Similar to zebrafish striated muscle cells, SMYD1-mediated MyHC methylation is essential for thick filament assembly but also homeostasis in human cardiomyocytes, indicating a conserved cross-species mechanism of Myosin regulation, first described nearly 40 years ago. Further research is now required to explore the therapeutic potential of targeting this pathway in cardiomyopathies and skeletal muscle disorders.
{"title":"SMYD1-mediated mono-methylation of lysine K35 of sarcomeric myosin heavy chain (MHC) regulates sarcomere assembly and homeostasis in zebrafish and human iPSC-derived cardiomyocytes","authors":"Federica Diofano , Chidinma Amadi , Larissa Hartmann , Bernd M. Gahr , Karolina Weinmann-Emhardt , Wolfgang Rottbauer , Steffen Just","doi":"10.1016/j.yjmcc.2025.09.002","DOIUrl":"10.1016/j.yjmcc.2025.09.002","url":null,"abstract":"<div><div>The SMYD family comprises a distinct class of lysine methyltransferases (KMTases) that methylate both histone and non-histone proteins. Among its five members (SMYD1–5), SMYD1 has been identified as a cardiac and skeletal muscle-specific KMTase that interacts with Myosin, in coordination with Unc45b and Hsp90a, to regulate thick filament assembly. However, the precise mechanism by which SMYD1 orchestrates Myosin assembly remains largely unknown.</div><div>Here, we demonstrate that SMYD1 physically associates with the N-terminal region of several myosin heavy chain (MyHC) isoforms and specifically catalyzes the mono-methylation of MyHC at lysine 35 (K35). Methylated MyHC is correctly incorporated into sarcomeres, whereas unmethylated MyHC in Smyd1-deficient zebrafish undergoes degradation <em>via</em> the ubiquitin-proteasome system (UPS), leading to defective thick filament assembly. Although UPS inhibition with MG132 restores Myosin levels in Smyd1-deficient zebrafish embryos, proper thick filament assembly remains impaired due to the absence of K35 MyHC mono-methylation.</div><div>Similar to zebrafish striated muscle cells, SMYD1-mediated MyHC methylation is essential for thick filament assembly but also homeostasis in human cardiomyocytes, indicating a conserved cross-species mechanism of Myosin regulation, first described nearly 40 years ago. Further research is now required to explore the therapeutic potential of targeting this pathway in cardiomyopathies and skeletal muscle disorders.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 74-84"},"PeriodicalIF":4.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.yjmcc.2025.09.005
Sayantan Jana , Shalabh Shukla , Nicole Sanford , Chloe Y. Lee , Abigail Regan , Li Liu , David A. Dichek
Background
Loeys-Dietz syndrome (LDS), caused by heterozygous loss-of-function mutations in members of transforming growth factor β (TGFβ) pathway, results in frequent aortic root aneurysms and type A dissections in human.
Methods
To unveil the mechanism of pathogenesis, the present study utilized single cell RNA sequencing (scRNAseq) from the proximal aortas (aortic root and ascending aorta) of 20 weeks old LDS (Tgfbr2G357W/+) and wild type (Tgfbr2+/+) mice. Histological and immunofluorescence studies were performed on 30 weeks old mice.
Results
ScRNAseq study identifies presence of an exclusive fibroblast population (remodeling fibroblasts) in the proximal aortas of LDS mice, which differentially expressed increased extracellular matrix remodeling genes (Mmp3, Col6a5, Col3a1, and Fn1), and macrophage recruiting chemokines (Saa3, Ccl7, Ccl8, and Cxcl11). These remodeling fibroblasts are focally localized with macrophages at the adventitia of dilated aortic roots of LDS mice. LDS aortas showed increased accumulation of Ccr2 expressing infiltrating macrophages, which are functionally involved in phagocytosis, immune responses and antigen processing and presentation. Ligand-receptor based interaction model recognizes remodeling fibroblasts as a major mediator for signaling communications with resident and recruited macrophages in the proximal aortopathies of LDS mice.
Conclusion
Our study highlights the presence of a specialized fibroblast population in the dilated aortic roots of LDS mice at 20 weeks and provides a deeper insight for involvement of remodeling fibroblasts in cellular heterogeneity and cell-cell communications in LDS aortopathies.
{"title":"Single cell analysis identifies a distinct population of fibroblasts that mediate increased cell-cell communication in murine aortopathy of Loeys-Dietz syndrome","authors":"Sayantan Jana , Shalabh Shukla , Nicole Sanford , Chloe Y. Lee , Abigail Regan , Li Liu , David A. Dichek","doi":"10.1016/j.yjmcc.2025.09.005","DOIUrl":"10.1016/j.yjmcc.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Loeys-Dietz syndrome (LDS), caused by heterozygous loss-of-function mutations in members of transforming growth factor β (TGFβ) pathway, results in frequent aortic root aneurysms and type A dissections in human.</div></div><div><h3>Methods</h3><div>To unveil the mechanism of pathogenesis, the present study utilized single cell RNA sequencing (scRNAseq) from the proximal aortas (aortic root and ascending aorta) of 20 weeks old LDS (<em>Tgfbr2</em><sup><em>G357W/+</em></sup>) and wild type (<em>Tgfbr2</em><sup><em>+/+</em></sup>) mice. Histological and immunofluorescence studies were performed on 30 weeks old mice.</div></div><div><h3>Results</h3><div>ScRNAseq study identifies presence of an exclusive fibroblast population (remodeling fibroblasts) in the proximal aortas of LDS mice, which differentially expressed increased extracellular matrix remodeling genes (<em>Mmp3, Col6a5, Col3a1, and Fn1</em>), and macrophage recruiting chemokines (<em>Saa3, Ccl7, Ccl8, and Cxcl11</em>). These remodeling fibroblasts are focally localized with macrophages at the adventitia of dilated aortic roots of LDS mice. LDS aortas showed increased accumulation of <em>Ccr2</em> expressing infiltrating macrophages, which are functionally involved in phagocytosis, immune responses and antigen processing and presentation. Ligand-receptor based interaction model recognizes remodeling fibroblasts as a major mediator for signaling communications with resident and recruited macrophages in the proximal aortopathies of LDS mice.</div></div><div><h3>Conclusion</h3><div>Our study highlights the presence of a specialized fibroblast population in the dilated aortic roots of LDS mice at 20 weeks and provides a deeper insight for involvement of remodeling fibroblasts in cellular heterogeneity and cell-cell communications in LDS aortopathies.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 60-73"},"PeriodicalIF":4.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11DOI: 10.1016/j.yjmcc.2025.08.012
Mark Boyett , Pan Li , Yirong Xiang , Henggui Zhang , Jae Kyoung Kim , Alicia D'Souza
This review concerns the mechanisms underlying the circadian rhythm in the electrical activity of the healthy heart. Attention is focussed on the circadian rhythm of the heart rate, the PR interval and the vulnerability to ventricular tachyarrhythmias, because they help to explain the circadian rhythm in the incidence of bradyarrhythmias, atrioventricular block, ventricular fibrillation and sudden cardiac death. Ultimately, all cardiac circadian rhythms are assumed to be extracardiac in origin, driven by a master circadian clock in the suprachiasmatic nucleus (SCN) in the hypothalamus and this review summarises our current understanding of how the SCN is responsible. The oldest explanation is that cardiac circadian rhythms are the result of an acute post-translational regulation of cardiac ion channels by the autonomic nervous system under the control of the SCN – this may be involved, but current evidence is controvertible. There is good evidence that rhythms in the transcription of cardiac ion channels are involved - driven by local circadian clocks in the heart and circadian rhythms in plasma catecholamines and glucocorticoid (all ultimately under the control of the SCN). There is also a plausible suggestion that the core body temperature under the control of the SCN is involved. Understanding the processes involved will potentially highlight new ways of treating cardiac arrhythmias – for example, recently, a glucocorticoid receptor blocker has been shown to prevent the morning increase in ventricular arrhythmia susceptibility in the mouse.
{"title":"Circadian determinants of heart rhythm and arrhythmias","authors":"Mark Boyett , Pan Li , Yirong Xiang , Henggui Zhang , Jae Kyoung Kim , Alicia D'Souza","doi":"10.1016/j.yjmcc.2025.08.012","DOIUrl":"10.1016/j.yjmcc.2025.08.012","url":null,"abstract":"<div><div>This review concerns the mechanisms underlying the circadian rhythm in the electrical activity of the healthy heart. Attention is focussed on the circadian rhythm of the heart rate, the PR interval and the vulnerability to ventricular tachyarrhythmias, because they help to explain the circadian rhythm in the incidence of bradyarrhythmias, atrioventricular block, ventricular fibrillation and sudden cardiac death. Ultimately, all cardiac circadian rhythms are assumed to be extracardiac in origin, driven by a master circadian clock in the suprachiasmatic nucleus (SCN) in the hypothalamus and this review summarises our current understanding of how the SCN is responsible. The oldest explanation is that cardiac circadian rhythms are the result of an acute post-translational regulation of cardiac ion channels by the autonomic nervous system under the control of the SCN – this may be involved, but current evidence is controvertible. There is good evidence that rhythms in the transcription of cardiac ion channels are involved - driven by local circadian clocks in the heart and circadian rhythms in plasma catecholamines and glucocorticoid (all ultimately under the control of the SCN). There is also a plausible suggestion that the core body temperature under the control of the SCN is involved. Understanding the processes involved will potentially highlight new ways of treating cardiac arrhythmias – for example, recently, a glucocorticoid receptor blocker has been shown to prevent the morning increase in ventricular arrhythmia susceptibility in the mouse.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 85-101"},"PeriodicalIF":4.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1016/j.yjmcc.2025.09.004
Sui-sui Wang , Xu Zhang , Ze-zhi Ke , Yu-xin Zeng , Xiu-yun Wen , Wen-bin Liu , Jie Zhao , Xiao-dong Zhuang , Li-zhen Liao
Objective
Activation of NLRP3 inflammasome contributes to cardiac aging progression. Klotho, a recognised anti-aging protein, exerts protective effects against cardiac aging. In this study, we aimed to elucidate the protective effects of Klotho on D-galactose (D-gal)-induced cardiac aging and the underlying mechanisms.
Methods
Aging severity in mice was evaluated based on coat condition and serum Klotho levels. Serum levels of interleukin (IL)-1β, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde were measured to assess cardiac oxidative stress and inflammatory response damage. Cardiac function was evaluated using echocardiography, whereas heart histopathological changes were observed through haematoxylin-eosin (HE) staining, Masson staining, and heart index. Cardiac aging was further assessed with β-galactosidase staining and western blot analysis of aging-related proteins (P53 and P21). Pyroptosis-related protein expression was assessed via western blot, and cardiac tissue reactive oxygen species (ROS) expression levels were determined through dihydroethidium staining. Similar analyses were conducted on D-gal-treated H9C2 cardiomyocytes.
Results
Compared to wild-type aged mice, Klotho-treated and NLRP3 knockout mice showed markedly reduced back hair loss, elevated serum Klotho and SOD levels, reduced serum IL-1β and LDH, enhanced left ventricular ejection fraction, left ventricular fractional shortening, peak E to peak A ratio, diminished heart size, cardiomyocyte hypertrophy and collagen deposition. Decreased cardiac aging markers, apoptosis-associated speck-like protein (ASC) formation, NLRP3 expression, cleaved-caspase-1, gasdermin D (GSDMD), IL-1β, and IL-18, and lower ROS levels were observed in cardiac tissues. These protective effects were abolished upon Nigericin injection.
Conclusions
Klotho delays D-gal-induced cardiac aging by regulating the ROS/NLRP3/pyroptosis pathway.
{"title":"Klotho attenuates D-galactose-induced cardiac aging through the ROS/NLRP3/pyroptosis pathway","authors":"Sui-sui Wang , Xu Zhang , Ze-zhi Ke , Yu-xin Zeng , Xiu-yun Wen , Wen-bin Liu , Jie Zhao , Xiao-dong Zhuang , Li-zhen Liao","doi":"10.1016/j.yjmcc.2025.09.004","DOIUrl":"10.1016/j.yjmcc.2025.09.004","url":null,"abstract":"<div><h3>Objective</h3><div>Activation of NLRP3 inflammasome contributes to cardiac aging progression. Klotho, a recognised anti-aging protein, exerts protective effects against cardiac aging. In this study, we aimed to elucidate the protective effects of Klotho on D-galactose (D-gal)-induced cardiac aging and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Aging severity in mice was evaluated based on coat condition and serum Klotho levels. Serum levels of interleukin (IL)-1β,<!--> <!-->lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde were measured to assess cardiac oxidative stress and inflammatory response damage. Cardiac function was evaluated using echocardiography, whereas heart histopathological changes were observed through haematoxylin-eosin (HE) staining, Masson staining, and heart index. Cardiac aging was further assessed with β-galactosidase staining and western blot analysis of aging-related proteins (P53 and P21). Pyroptosis-related protein expression was assessed via western blot, and cardiac tissue reactive oxygen species (ROS) expression levels were determined through dihydroethidium staining. Similar analyses were conducted on D-gal-treated H9C2 cardiomyocytes.</div></div><div><h3>Results</h3><div>Compared to wild-type aged mice, Klotho-treated and NLRP3 knockout mice showed markedly reduced back hair loss, elevated serum Klotho and SOD levels, reduced serum IL-1β and LDH, enhanced left ventricular ejection fraction, left ventricular fractional shortening, peak E to peak A ratio, diminished heart size, cardiomyocyte hypertrophy and collagen deposition. Decreased cardiac aging markers, apoptosis-associated speck-like protein (ASC) formation, NLRP3 expression, cleaved-caspase-1, gasdermin D (GSDMD), IL-1β, and IL-18, and lower ROS levels were observed in cardiac tissues. These protective effects were abolished upon Nigericin injection.</div></div><div><h3>Conclusions</h3><div>Klotho delays D-gal-induced cardiac aging by regulating the ROS/NLRP3/pyroptosis pathway.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 35-48"},"PeriodicalIF":4.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.yjmcc.2025.09.003
Alex Gallinat, Xisheng Li, Nikhil P. Raisinghani, Sabrina La Salvia, Anh Phan, Shihong Zhang, Spyros A. Mavropoulos, Samta Veera, Seonghun Yoon, Kiyotake Ishikawa, Susmita Sahoo
Selective therapeutic targeting of cardiomyocytes (CMs) and non-myocytes (NMs) within the heart is an active field of research. The success of those novel therapeutic strategies is linked to the ability to accurately assess uptake and gene delivery efficiencies in clinically relevant animal models. Nevertheless, quantification at the single cell level remains a significant challenge. While flow cytometry offers the possibility of an accurate and direct single-cell quantification, the unique structural and physical properties of CMs complicate the analysis. There are no standardized methods reported for the flow cytometry analysis of adult CMs, which is a significant pitfall in the field. Here, we address this gap and introduce a robust and optimized method for the successful flow cytometry analysis of isolated CMs. Starting from tissue digestion, we present a simple workflow for the isolation and characterization of CMs and NMs, tested and validated for pig and mouse. We demonstrate the versatility of this method through three biologically relevant applications. First, we introduce a model to quantify CMs nucleation based on DNA content distribution. Second, we assess cell-specific in vivo gene delivery with AAV-Luc in pig hearts. And last, we demonstrate how structural remodeling of CMs affects their light scattering properties, in a pressure overload-induced hypertrophy mouse model. Together, these findings establish a flexible and quantitative platform for single-cell analysis of cardiac cell populations in both basic and translational cardiovascular research.
{"title":"Flow cytometry of the myocardium: An end-to-end analysis of adult cardiomyocytes isolated from pig and mouse hearts","authors":"Alex Gallinat, Xisheng Li, Nikhil P. Raisinghani, Sabrina La Salvia, Anh Phan, Shihong Zhang, Spyros A. Mavropoulos, Samta Veera, Seonghun Yoon, Kiyotake Ishikawa, Susmita Sahoo","doi":"10.1016/j.yjmcc.2025.09.003","DOIUrl":"10.1016/j.yjmcc.2025.09.003","url":null,"abstract":"<div><div>Selective therapeutic targeting of cardiomyocytes (CMs) and non-myocytes (NMs) within the heart is an active field of research. The success of those novel therapeutic strategies is linked to the ability to accurately assess uptake and gene delivery efficiencies in clinically relevant animal models. Nevertheless, quantification at the single cell level remains a significant challenge. While flow cytometry offers the possibility of an accurate and direct single-cell quantification, the unique structural and physical properties of CMs complicate the analysis. There are no standardized methods reported for the flow cytometry analysis of adult CMs, which is a significant pitfall in the field. Here, we address this gap and introduce a robust and optimized method for the successful flow cytometry analysis of isolated CMs. Starting from tissue digestion, we present a simple workflow for the isolation and characterization of CMs and NMs, tested and validated for pig and mouse. We demonstrate the versatility of this method through three biologically relevant applications. First, we introduce a model to quantify CMs nucleation based on DNA content distribution. Second, we assess cell-specific <em>in vivo</em> gene delivery with AAV-Luc in pig hearts. And last, we demonstrate how structural remodeling of CMs affects their light scattering properties, in a pressure overload-induced hypertrophy mouse model. Together, these findings establish a flexible and quantitative platform for single-cell analysis of cardiac cell populations in both basic and translational cardiovascular research.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 49-59"},"PeriodicalIF":4.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.yjmcc.2025.09.001
Yilian Wang , Pieterjan Dierickx
Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.
{"title":"Circadian transcriptional repressors REV-ERBα/β and E4BP4 regulate cardiac function","authors":"Yilian Wang , Pieterjan Dierickx","doi":"10.1016/j.yjmcc.2025.09.001","DOIUrl":"10.1016/j.yjmcc.2025.09.001","url":null,"abstract":"<div><div>Circadian rhythms are an endogenous timekeeping system with a period of approximately 24 h that regulate many aspects of body physiology to maintain organismal health. Dysregulation of circadian rhythmicity has been implicated in various human diseases such as cancer as well as metabolic and cardiovascular disorders. Intrinsic, biological oscillations are regulated by the circadian clock, a molecular transcriptional/translational feedback loop that involves activators such as BMAL1 and CLOCK, and repressors such as REV-ERBα/β and E4BP4. Recent studies have shown that REV-ERBs and E4BP4 play a key role in regulating cardiac gene expression programs and metabolism. Here, we discuss these findings and highlight the mechanisms of their role in healthy and diseased hearts. Since REV-ERBs are drug targets, they hold potential for the treatment of cardiovascular disorders that are linked to circadian dysregulation or metabolic imbalance.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 23-31"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-26DOI: 10.1016/j.yjmcc.2025.08.010
Shuliang Guo , Yingwei Liu , Angela Ryan , Ana Laura Lopez Serrano , Isabelle Deschenes , Jihyun Jang , Deqiang Li
Establishment and maintenance of specialized CMs in the heart is critical for the proper cardiac structure and function. Conversely, loss or gain of their identities is associated with various heart diseases such as cardiac arrythmia and cardiomyopathy. CM identity is established during early heart development and continues to be maintained under normal physiological condition, and this is predominantly accomplished by gene regulation. Our understanding of potential genetic, epigenetic or posttranscriptional programs that regulate CM identity (e.g., atrial or ventricular CM identity) is still quite limited. To this end, we summarize current understandings on atrial and ventricular CM identity regulations and discuss potential future research directions to unveil the underlying regulatory mechanisms.
{"title":"Regulation of atrial and ventricular cardiomyocyte identity","authors":"Shuliang Guo , Yingwei Liu , Angela Ryan , Ana Laura Lopez Serrano , Isabelle Deschenes , Jihyun Jang , Deqiang Li","doi":"10.1016/j.yjmcc.2025.08.010","DOIUrl":"10.1016/j.yjmcc.2025.08.010","url":null,"abstract":"<div><div>Establishment and maintenance of specialized CMs in the heart is critical for the proper cardiac structure and function. Conversely, loss or gain of their identities is associated with various heart diseases such as cardiac arrythmia and cardiomyopathy. CM identity is established during early heart development and continues to be maintained under normal physiological condition, and this is predominantly accomplished by gene regulation. Our understanding of potential genetic, epigenetic or posttranscriptional programs that regulate CM identity (e.g., atrial or ventricular CM identity) is still quite limited. To this end, we summarize current understandings on atrial and ventricular CM identity regulations and discuss potential future research directions to unveil the underlying regulatory mechanisms.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 11-22"},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-21DOI: 10.1016/j.yjmcc.2025.08.009
Yin Wang , Di Ren , Randy Kang , Kai Zhang , Yunqian Peng , Heather Zhou , Geming Lu , Junjie Guo , Adolfo Garcia-Ocaña , Yingfeng Deng , June-Wha Rhee , Zhao V. Wang
The emergence of single nucleus multiome sequencing (snMultiome-seq) technology has greatly advanced our understanding of various biological processes. However, existing experimental protocols fail to isolate high-quality nuclei from cryopreserved fibrous tissues, such as the heart, leading to low-quality downstream sequencing data. Here, we develop a simple and inexpensive approach for nuclei isolation from frozen tissues, named douncer-filter-gradient-centrifugation (DFGC). This protocol takes approximately 1.5 h to complete, including mincing (1 min), douncing (3 min), filtration (20 min), and density gradient centrifugation (40 min). To evaluate the effectiveness of the DFGC approach, we compare it with two commonly used methods for nuclei isolation – micro-beads and fluorescence-activated cell sorting (FACS). We demonstrate that the DFGC method performs in a preferred manner for the generation of both single nucleus gene expression and chromatin transposase accessibility data. We anticipate the DFGC method to be a mainstream approach for high-quality nuclei isolation in snMultiome-seq.
{"title":"A simple approach of nuclei isolation for single nucleus multiome sequencing","authors":"Yin Wang , Di Ren , Randy Kang , Kai Zhang , Yunqian Peng , Heather Zhou , Geming Lu , Junjie Guo , Adolfo Garcia-Ocaña , Yingfeng Deng , June-Wha Rhee , Zhao V. Wang","doi":"10.1016/j.yjmcc.2025.08.009","DOIUrl":"10.1016/j.yjmcc.2025.08.009","url":null,"abstract":"<div><div>The emergence of single nucleus multiome sequencing (snMultiome-seq) technology has greatly advanced our understanding of various biological processes. However, existing experimental protocols fail to isolate high-quality nuclei from cryopreserved fibrous tissues, such as the heart, leading to low-quality downstream sequencing data. Here, we develop a simple and inexpensive approach for nuclei isolation from frozen tissues, named douncer-filter-gradient-centrifugation (DFGC). This protocol takes approximately 1.5 h to complete, including mincing (1 min), douncing (3 min), filtration (20 min), and density gradient centrifugation (40 min). To evaluate the effectiveness of the DFGC approach, we compare it with two commonly used methods for nuclei isolation – micro-beads and fluorescence-activated cell sorting (FACS). We demonstrate that the DFGC method performs in a preferred manner for the generation of both single nucleus gene expression and chromatin transposase accessibility data. We anticipate the DFGC method to be a mainstream approach for high-quality nuclei isolation in snMultiome-seq.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"208 ","pages":"Pages 1-10"},"PeriodicalIF":4.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-20DOI: 10.1016/j.yjmcc.2025.08.007
Brijesh Sathian, Javed Iqbal, Syed Muhammad Ali
{"title":"Cytoplasmic RBM20 gain-of-function induces atrial arrhythmogenicity independent of splicing defects in a novel murine model","authors":"Brijesh Sathian, Javed Iqbal, Syed Muhammad Ali","doi":"10.1016/j.yjmcc.2025.08.007","DOIUrl":"10.1016/j.yjmcc.2025.08.007","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"207 ","pages":"Page 92"},"PeriodicalIF":4.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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