Role of Epigenetics in Chronic Lung Disease DOI Creative Commons
Felix Ritzmann,

Michelle Brand,

Robert Bals

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 251 - 251

Published: Feb. 10, 2025

Epigenetics regulates gene expression and thus cellular processes that underlie the pathogenesis of chronic lung diseases such as obstructive pulmonary disease (COPD), asthma, idiopathic fibrosis (IPF). Environmental factors (e.g., air pollution, smoking, infections, poverty), but also conditions gastroesophageal reflux, induce epigenetic changes long before is diagnosed. Therefore, signatures have potential to serve biomarkers can be used identify younger patients who are at risk for premature loss function or IPF. Epigenetic analyses contribute a better understanding disease. This directly improve therapies, well development innovative drugs. Here, we highlight role epigenetics in progression disease, with focus on DNA methylation.

Language: Английский

Fibroblast and myofibroblast activation in normal tissue repair and fibrosis DOI
Fereshteh S. Younesi, Andrew Miller, Thomas H. Barker

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 617 - 638

Published: April 8, 2024

Language: Английский

Citations

165
Engineered hydrogels for mechanobiology DOI
Ulrich Blache, Eden M. Ford, Byung Hang Ha

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Dec. 15, 2022

Language: Английский

Citations

120
Cardiac fibroblasts and mechanosensation in heart development, health and disease DOI
Maurizio Pesce, Georg N. Duda, Giancarlo Forte

et al.

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(5), P. 309 - 324

Published: Nov. 14, 2022

Language: Английский

Citations

77
Mechanical forces across compartments coordinate cell shape and fate transitions to generate tissue architecture DOI Creative Commons
Clémentine Villeneuve, Ali Hashmi, Irene Ylivinkka

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(2), P. 207 - 218

Published: Feb. 1, 2024

Abstract Morphogenesis and cell state transitions must be coordinated in time space to produce a functional tissue. An excellent paradigm understand the coupling of these processes is mammalian hair follicle development, which initiated by formation an epithelial invagination—termed placode—that coincides with emergence designated stem population. The mechanisms directing deformation epithelium, physical compartmentalization placode are unknown. Here we identify key role for mechanical forces stemming from contractile, proliferative proteolytic activities across mesenchymal compartments generating structure. A ring fibroblast cells gradually wraps around generate centripetal contractile forces, which, collaboration polarized myosin activity, promote elongation local tissue thickening. These stresses further enhance Sox9 expression positioning. Subsequently, remodelling locally softens basement membrane facilitate release pressure on placode, enabling localized divisions, fluidification invagination into underlying mesenchyme. Together, our experiments modelling dynamic shape transformations tissue-scale cooperation as factors orchestrating organ formation.

Language: Английский

Citations

41
Mechanical state transitions in the regulation of tissue form and function DOI
Yanlan Mao, Sara A. Wickström

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(8), P. 654 - 670

Published: April 10, 2024

Language: Английский

Citations

34
Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity DOI Creative Commons
Amy R. Strom, Yoonji Kim, Hongbo Zhao

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5282 - 5297.e20

Published: Aug. 20, 2024

Biomolecular condensates assemble in living cells through phase separation and related transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with other cellular structures, including membranes, cytoskeleton, DNA RNA, membraneless compartments. These are expected to give rise capillary forces, but there few ways quantifying harnessing forces cells. Here, we introduce viscoelastic chromatin tethering organization (VECTOR), which uses light-inducible biomolecular generate at targeted loci. VECTOR can be utilized programmably reposition genomic loci on a timescale seconds minutes, quantitatively revealing local heterogeneity the material properties chromatin. synthetic built from components naturally liquid-like structures cells, highlighting potential role for native do work reorganize genome impact architecture.

Language: Английский

Citations

27
Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces DOI Creative Commons
Patrizia Romani, Giada Benedetti, Martina Cusan

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(12), P. 2046 - 2060

Published: Oct. 21, 2024

Tissue-scale architecture and mechanical properties instruct cell behaviour under physiological diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that extracellular matrix stiffness, spatial confinements applied forces, including stretching mouse skin, regulate mitochondrial dynamics. Actomyosin tension promotes phosphorylation elongation factor 1 (MIEF1), limiting recruitment dynamin-related protein (DRP1) at mitochondria, as well peri-mitochondrial F-actin formation fission. Strikingly, fission is also a general mechanotransduction mechanism. Indeed, found DRP1- MIEF1/2-dependent required sufficient to three transcription factors broad relevance-YAP/TAZ, SREBP1/2 NRF2-to control proliferation, lipogenesis, antioxidant metabolism, chemotherapy resistance adipocyte differentiation in response cues. This extends liver, where DRP1 regulates hepatocyte proliferation identity-hallmark YAP-dependent phenotypes. We propose mitochondria fulfil unifying signalling function by which tissue microenvironment coordinates complementary functions.

Language: Английский

Citations

19
Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus DOI Creative Commons

Xiaojing Liu,

Man Zhang, Peng Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(10)

Published: March 5, 2025

Cells respond to adhesive ligands such as arginine-glycine-aspartate (RGD) through integrins, which regulates cellular activities via influencing cytoskeleton assembly. Herein, we report that the nanoscale distribution of active on biomaterials cells not only cytoplasmic tension but also nuclear tension. This is particularly related translocation actin into nucleus and highlighted in our interpretation an "abnormal" phenomenon large RGD nanospacing (>70 nm) disassembles integrin clusters, inhibits cell adhesion, promotes osteogenic differentiation mesenchymal stem cells. Our studies reveal unstable adhesion at 150 nm distance increases dynamics, resulting globular (G) actin. The compartment polymerization more G-actins filamentous actins tension, facilitating transcription activity releasing calcium ions from endoplasmic reticulum. noncanonical mechanotransduction process sheds insight pertinent cell-material interactions.

Language: Английский

Citations

3
Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz DOI Creative Commons
Dakota L. Jones, Grey F. Hallström, Xi Jiang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(22)

Published: May 22, 2023

Cells integrate mechanical cues to direct fate specification maintain tissue function and homeostasis. While disruption of these is known lead aberrant cell behavior chronic diseases, such as tendinopathies, the underlying mechanisms by which signals are not well understood. Here, we show using a model tendon de-tensioning that loss tensile in vivo acutely changes nuclear morphology, positioning, expression catabolic gene programs, resulting subsequent weakening tendon. In vitro studies paired ATAC/RNAseq demonstrate cellular tension rapidly reduces chromatin accessibility vicinity Yap/Taz genomic targets while also increasing genes involved matrix catabolism. Concordantly, depletion elevates expression. Conversely, overexpression Yap results reduction at loci, reducing transcriptional levels. The only prevents induction this broad program following tension, but preserves state from force-induced alterations. Taken together, provide novel mechanistic details mechanoepigenetic regulate through axis.

Language: Английский

Citations

34
Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma DOI Creative Commons

Jingwei Cai,

Tianyi Chen, Zhiyu Jiang

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(7), P. 2114 - 2131

Published: Jan. 1, 2023

Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). samples were classified into three heterogeneous pathway subtypes with different profiles: Cluster 1, an ECM-producing subtype upregulated glycan metabolism; 2, a hybrid partial dysregulation. 3, lipogenic lipid These prognosis, clinical features genomic alterations. identified key enzymes that respond to regulate metabolism through bioinformatic analysis. found long-chain acyl-CoA dehydrogenase (ACADL) is mechanoreactive enzyme reprograms cell response extracellular stiffness. ACADL also regarded as tumor suppressor HCC. increased led activation of Yes-associated protein (YAP) YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able directly repress at level. The ACADL-dependent mechanoresponsive potential therapeutic target for treatment.

Language: Английский

Citations

30