Adult mammals are susceptible to substantial cardiomyocyte (CM) loss following various cardiac diseases due to the limited capacity of CM proliferation and regeneration. Recently, direct cardiac reprogramming, converting fibroblasts into induced CMs, has been achieved both in vitro and in vivo through forced expression of transcription factors (TFs). This review encapsulates the advancements made in enhancing reprogramming efficiency and underlying molecular mechanisms. It covers the optimization of TF-based reprogramming cocktails and in vivo delivery platform and recently identified regulators in enhancing reprogramming efficiency. In addition, we discuss recent insights into the molecular mechanisms of direct cardiac reprogramming from single-cell omics analyses. Finally, we briefly touch on remaining challenges and prospective direction of this field.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.gde.2024.102226 | DOI Listing |
Am J Physiol Lung Cell Mol Physiol
January 2025
Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, IL 60637.
Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that TGF-β-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote metabolic reprogramming in lung fibroblasts characterized by upregulation of the de synthesis of glycine, the most abundant amino acid found in collagen protein. Whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Escuela de Tecnología Médica, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
Preeclampsia (PE) is a complex pregnancy syndrome characterized by hypertension with or without proteinuria, affecting 2-6% of pregnancies globally. PE is characterized by excessive release of damage-associated molecular patterns (DAMPs) into the maternal circulation. This DAMP-rich milieu acts on innate immune cells, inducing a proinflammatory state characterized by elevated cytokines such as IL-1β and IL-18.
View Article and Find Full Text PDFNat Commun
December 2024
Center for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation.
View Article and Find Full Text PDFJ Mol Cell Cardiol
December 2024
Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen 518057, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; Key Laboratory of Application of Pluripotent Stem Cells in Heart Regeneration, Chinese Academy of Medical Sciences, Beijing 100037, China. Electronic address:
Background: Our previous single-cell RNA sequencing study in the adult human heart revealed that cardiomyocytes from both the atrium and ventricle display high activities of Krüppel-like factor 2 (KLF2) regulons. However, the role of the transcription factor KLF2 in cardiomyocyte biology remains largely unexplored.
Methods And Results: We employed transverse aortic constriction surgery in male C57BL/6 J mice to develop an in vivo model of cardiac hypertrophy, and generated different in vitro cardiac hypertrophy models in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes.
J Proteomics
December 2024
School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia; Department of Medicine, University of Otago, Christchurch 8014, New Zealand; Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand. Electronic address:
Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female mdx mice were phenotypically stratified into "stress-resistant" or "stress-sensitive" groups based on their response to two laboratory stressors.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!