YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes DOI
Vladimír Vinarský, Stefania Pagliari, Fabiana De Martino

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

Abstract Background Perspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown improve heart regeneration after myocardial infarction, possibly by expanding pool of cardiomyocytes. We hypothesized that activating pathway’s downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human therefore investigated how YAP1 influences cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response mechanical stimuli, intracellular Ca 2+ ″ dynamics and force development using models cardiomyocytes derived from pluripotent stem cells. Methods employed genetic deficient embryonic induced cells, differentiation, compliant cultivation substrates, actuation, ECM deposition, super resolution microscopy, measurements engineered tissues (EHTs) characterize deficiency during maturation. also used full length re- expression rescue contracting Results contributes participates formation alignment myofibrils, as well maturation properties. The net effect is inability respond physiological stimuli compensatory growth resulting reduced development. Additionally, reactivation leads myofibril Conclusions This research demonstrates activity essential promote contractility, inducing stimuli.

Language: Английский

Functions of RNA-Binding Proteins in Cardiovascular Disease DOI Creative Commons
Grégoire Ruffenach,

Lejla Medzikovic,

Wasila Sun

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(24), P. 2794 - 2794

Published: Dec. 8, 2023

Gene expression is under tight regulation from the chromatin structure that regulates gene accessibility by transcription machinery to protein degradation. At transcript level, this falls on RNA-binding proteins (RBPs). RBPs are a large and diverse class of involved in all aspects transcript’s lifecycle: splicing maturation, localization, stability, translation. In past few years, our understanding role cardiovascular diseases has expanded. Here, we discuss general function latest discoveries their pulmonary systemic diseases.

Language: Английский

Citations

4
M6A modification in cardiovascular disease: With a focus on programmed cell death DOI Creative Commons
Wen Li, Yao Liu,

Ruiyan Xu

et al.

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(5), P. 101039 - 101039

Published: July 14, 2023

N

Language: Английский

Citations

3
Liquid–Liquid Phase Separation Sheds New Light upon Cardiovascular Diseases DOI Open Access

Ziyang Cai,

Shuai Mei,

Zhou Li

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15418 - 15418

Published: Oct. 21, 2023

Liquid-liquid phase separation (LLPS) is a biophysical process that mediates the precise and complex spatiotemporal coordination of cellular processes. Proteins nucleic acids are compartmentalized into micron-scale membrane-less droplets via LLPS. These droplets, termed biomolecular condensates, highly dynamic, have concentrated components, perform specific functions. Biomolecular condensates been observed to organize diverse key biological processes, including gene transcription, signal transduction, DNA damage repair, chromatin organization, autophagy. The dysregulation these activities owing aberrant LLPS important in cardiovascular diseases. This review provides detailed overview regulation functions comprehensive depiction several common diseases, discusses revolutionary therapeutic perspective modulating diseases new treatment strategies relevant

Language: Английский

Citations

3
Regulation of protein synthesis and stability by mechanical cues and its implications in cancer DOI Creative Commons
Sara Göransson, Staffan Strömblad

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 86, P. 102304 - 102304

Published: Dec. 18, 2023

Elevated tissue stiffness is a common feature of many solid tumors and the downstream mechanical signaling affects cellular processes contributes to cancer progression. Significant progress has been made in understanding how properties matrix affect cell behavior as well transcription. However, same cues impact protein synthesis stability this may contribute disease less understood. Here, we present emerging evidence that progression frequently supported by gene regulation acting beyond mRNA level highlight some known crosstalk between type mechanotransduction other contexts. We suggest future systematic approaches define mechanosensitive translatomes proteomes these are controlled provide novel targets for therapy.

Language: Английский

Citations

2
irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein associations on RNA DOI
Luca Ducoli,

Brian Zarnegar,

Douglas F. Porter

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 28, 2024

RNA binding proteins ( RBPs ) control varied processes, including splicing, stability, transport, and translation

Language: Английский

Citations

0
m6A Ribonucleic Acid Methylation in Fibrotic Diseases of Visceral Organs DOI Creative Commons

Xiaoniu Dai,

Yusi Cheng, Wei Luo

et al.

Small Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Fibrosis is a pathological process characterized by the excessive deposition of extracellular matrix in tissue's space, leading to structural injury and organ dysfunction, even failure, posing threat human life. Despite mounting evidence suggesting that fibrosis reversible, effective treatments for fibrotic diseases are lacking. Accumulating has elucidated ribonucleic acid (RNA) modifications have emerged as novel mechanisms regulating gene expression. N6‐methyladenosine (m6A) modification well‐known prevalent RNA posttranscriptional participates essential biological processes such splicing, translation, degradation. It tightly implicated wide range cellular various diseases, particularly fibrosis. The m6A dynamic reversible regulated methylases, commonly known “writers,” demethylases referred “erasers,” while recognized “readers.” suggests on RNAs associated with visceral organs including lungs, heart, liver, kidney. In this review, recent advances impact methylation highlighted potential prospects therapy treating discussed.

Language: Английский

Citations

0
An iPSC-derived bio-inspired scaffold modelling the structure and the effects of extracellular matrix in cardiac fibrosis DOI Creative Commons
Francesco Niro, Soraia Fernandes, Marco Cassani

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Cardiac fibrosis occurs following insults to the myocardium and is characterized by abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte contractile activity eventually leads heart failure. This phenomenon driven differentiation cardiac fibroblasts (cFbs) into myofibroblasts results in changes ECM biochemical, structural mechanical properties. The lack predictive vitro models has so far hampered search for innovative treatments. Here, we devised a single-step decellularization protocol obtain thoroughly characterize biochemical micro-mechanical properties secreted activated cFbs differentiated from human induced pluripotent stem cells (iPSCs). We iPSC-derived myofibroblast phenotype tuning basic fibroblast growth factor (bFGF) transforming beta 1 (TGF-β1) signalling confirmed that acquired key features phenotype, like SMAD2/3 nuclear shuttling, formation aligned alpha-smooth muscle actin (α−SMA)-rich stress fibres increased focal adhesions (FAs) assembly. Next, used Mass Spectrometry, nanoindentation, scanning electron confocal microscopy unveil characteristic composition visco-elastic abundant, collagen-rich deposited . Finally, demonstrated fibrotic activates mechanosensitive pathways cardiomyocytes, impacting on their shape, sarcomere alignment, calcium handling thus propose bio-inspired decellularized matrices as animal-free, isogenic culture substrates recapitulating pathophysiological occurring at cellular level during fibrosis.

Language: Английский

Citations

0
m6A Reader HNRNPC Facilitates Adipogenesis by Regulating Cytoskeletal Remodeling through Enhanced Lcp1 mRNA Stability DOI Creative Commons

Wenhua Xie,

Yewei Cui,

Lingzhi Yue

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Reduced adipogenesis is a prominent characteristic of aging adipose tissue and closely tied to the development metabolic disorders associated with aging. Epigenetic modification plays crucial role in process, yet N6-methyladenosine (m6A), most prevalent RNA modification, regulating remains uncertain. Our study found that levels m6A its recognition protein, heterogeneous nuclear ribonucleoprotein C (HNRNPC), decrease as individuals age. Lower HNRNPC were also linked reduced during Through loss gain function experiments HNRNPC, we established positive correlation between vitro. Hnrnpc-APKO mice displayed decreased adipogenesis, increased insulin resistance, elevated expression aging-related inflammation-related genes, lipogenesis-related other compared their littermates. Additionally, discovered facilitated stability lymphocyte cytosolic protein 1 (Lcp1) mRNA by binding motif LCP1. Overexpression LCP1 mitigated inhibition caused through modulation cytoskeletal remodeling. Finally, our findings demonstrate anti-aging treatments could enhance levels. In conclusion, positively aging, increacing highlights potential therapeutic target for addressing imbalances related

Language: Английский

Citations

0
YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes DOI
Vladimír Vinarský, Stefania Pagliari, Fabiana De Martino

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

Abstract Background Perspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown improve heart regeneration after myocardial infarction, possibly by expanding pool of cardiomyocytes. We hypothesized that activating pathway’s downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human therefore investigated how YAP1 influences cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response mechanical stimuli, intracellular Ca 2+ ″ dynamics and force development using models cardiomyocytes derived from pluripotent stem cells. Methods employed genetic deficient embryonic induced cells, differentiation, compliant cultivation substrates, actuation, ECM deposition, super resolution microscopy, measurements engineered tissues (EHTs) characterize deficiency during maturation. also used full length re- expression rescue contracting Results contributes participates formation alignment myofibrils, as well maturation properties. The net effect is inability respond physiological stimuli compensatory growth resulting reduced development. Additionally, reactivation leads myofibril Conclusions This research demonstrates activity essential promote contractility, inducing stimuli.

Language: Английский

Citations

0