Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation DOI Creative Commons
Joana Silva, Ferhat Alkan, Sofia Ramalho

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 2, 2022

Abstract The small intestine is a rapidly proliferating organ that maintained by population of Lgr5 -expressing intestinal stem cells (ISCs). However, several -negative ISC populations have been identified, and this remarkable plasticity allows the to respond both local environment damage. mediators such are still largely unknown. Using organoids mouse models, we show upon ribosome impairment (driven Rptor deletion, amino acid starvation, or low dose cyclohexamide treatment) ISCs gain an -negative, fetal-like identity. This accompanied rewiring metabolism. Our findings suggest can act as sensor nutrient availability, allowing environment. Mechanistically, phenotype requires activation ZAKɑ, which in turn activates YAP, via SRC. Together, our data reveals central role for dynamics cells, identify ZAKɑ critical mediator cell

Language: Английский

Mechanics of 3D Cell–Hydrogel Interactions: Experiments, Models, and Mechanisms DOI
Franck J. Vernerey, Shankar Lalitha Sridhar, Archish Muralidharan

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(18), P. 11085 - 11148

Published: Sept. 2, 2021

Hydrogels are highly water-swollen molecular networks that ideal platforms to create tissue mimetics owing their vast and tunable properties. As such, hydrogels promising cell-delivery vehicles for applications in engineering have also emerged as an important base ex vivo models study healthy pathophysiological events a carefully controlled three-dimensional environment. Cells readily encapsulated resulting plethora of biochemical mechanical communication mechanisms, which recapitulates the natural cell extracellular matrix interaction tissues. These interactions complex, with multiple invariably coupled spanning length time scales. To identify underlying mechanisms involved, integrated experimental computational approach is ideally needed. This review discusses state our knowledge on cell–hydrogel interactions, focus mechanics transport, this context, highlights recent advancements experiments, mathematical modeling. The begins background thermodynamics physics fundamentals govern hydrogel transport. focuses two main classes hydrogels, described semiflexible polymer represent physically cross-linked fibrous flexible representing chemically synthetic hydrogels. In review, we highlight five involve key cellular functions related communication, mechanosensing, migration, growth, deposition elaboration. For each these functions, experiments most up date modeling strategies discussed then followed by summary how tune properties achieve desired functional outcome. We conclude linking make case need integrate advance fundamental understanding cell–matrix will ultimately help new therapeutic approaches enable successful engineering.

Language: Английский

Citations

112
Insights into recent findings and clinical application of YAP and TAZ in cancer DOI
James Franklin, ZhengMing Wu, Kun‐Liang Guan

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(8), P. 512 - 525

Published: June 12, 2023

Language: Английский

Citations

112
The influence of nanotopography on cell behaviour through interactions with the extracellular matrix – A review DOI Creative Commons
Jiajun Luo, Matthew Walker, Yinbo Xiao

et al.

Bioactive Materials, Journal Year: 2021, Volume and Issue: 15, P. 145 - 159

Published: Dec. 21, 2021

Nanotopography presents an effective physical approach for biomaterial cell manipulation mediated through material-extracellular matrix interactions. The extracellular that exists in the cellular microenvironment is crucial guiding behaviours, such as determination of integrin ligation and interaction with growth factors. These interactions regulate downstream mechanotransductive pathways, rearrangements cytoskeleton activation signal cascades. Protein adsorption onto nanotopography strongly influences conformation distribution density and, therefore, subsequent responses. In this review, we first discuss interactive mechanisms protein on nanotopography. Secondly, summarise advances creating nanotopographical features to instruct desired behaviours. Lastly, focus pathways initiated by This review provides overview current state-of-the-art designs aiming provide better biomedical materials future.

Language: Английский

Citations

109
Nuclear compression regulates YAP spatiotemporal fluctuations in living cells DOI Creative Commons
Newsha Koushki, Ajinkya Ghagre, Luv Kishore Srivastava

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(28)

Published: July 3, 2023

Yes-associated protein (YAP) is a key mechanotransduction in diverse physiological and pathological processes; however, ubiquitous YAP activity regulatory mechanism living cells has remained elusive. Here, we show that nuclear translocation highly dynamic during cell movement driven by compression arising from contractile work. We resolve the mechanistic role of cytoskeletal contractility manipulation mechanics. Disrupting linker nucleoskeleton cytoskeleton complex reduces for given correspondingly decreases localization. Conversely, decreasing stiffness via silencing lamin A/C increases Finally, using osmotic pressure, demonstrated even without active myosin or filamentous actin regulates The relationship between localization captures universal regulation with broad implications health biology.

Language: Английский

Citations

45
Extracellular matrix: Dystroglycan interactions—Roles for the dystrophin‐associated glycoprotein complex in skeletal tissue dynamics DOI Creative Commons
Mark Hopkinson, Andrew A. Pitsillides

International Journal of Experimental Pathology, Journal Year: 2025, Volume and Issue: 106(2)

Published: Feb. 8, 2025

Contributions made by the dystrophin-associated glycoprotein complex (DGC) to cell-cell and cell-extracellular matrix (ECM) interactions are vital in development, homeostasis pathobiology. This review explores how DGC functions may extend skeletal pathophysiology appraising known roles of its major ECM ligands, likely associated signalling pathways, regulating cartilage bone cell behaviour emergent phenotypes. These considerations will be contextualised highlighting potential studies into role isolated chondrocytes, osteoblasts osteoclasts, fuller deliberation phenotypes that emerge very young mice lacking vital, yet diverse core elements DGC. Our points for individual components-including glycosylation dystroglycan itself-beyond establishment membrane stability which clearly accounts severe muscle muscular dystrophy. It implies short stature, low mineral density, poor health greater fracture risk these patients, has been attributed due primary deficiencies muscle-evoked loading, instead arise controlling tissue (re)modelling.

Language: Английский

Citations

2
Decellularized extracellular matrix mediates tissue construction and regeneration DOI Creative Commons
Chuanqi Liu, Ming Pei, Qingfeng Li

et al.

Frontiers of Medicine, Journal Year: 2021, Volume and Issue: 16(1), P. 56 - 82

Published: Dec. 28, 2021

Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide with three-dimensional (3D) structural integrity cellular-function regulation. Containing the crucial traits of cellular microenvironment, ECM substitutes mediate cell-matrix interactions prompt stem-cell proliferation differentiation for 3D organoid construction in vitro or regeneration vivo. However, these ECMs are often applied generically have yet be extensively developed specific cell types cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular improves culture development remodeling during wound healing after implantation into host as well. Gaining better insight derived from either that regulate reconstruction helps us select, produce, implant most suitable thus promote vivo regeneration. Overall, decellularization methodologies tissue/cell-derived scaffolds cellular-growth supplements used propagation discussed. Moreover, current preclinical applications by which components modulate wound-healing process reviewed.

Language: Английский

Citations

92
Signaling network regulating osteogenesis in mesenchymal stem cells DOI
Sachin Thomas,

Bithiah Grace Jaganathan

Journal of Cell Communication and Signaling, Journal Year: 2021, Volume and Issue: 16(1), P. 47 - 61

Published: July 8, 2021

Language: Английский

Citations

77
YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia DOI Creative Commons
Joshua Hatterschide, Paola A. Castagnino, Hee Won Kim

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Feb. 16, 2022

Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative at same anatomical site, prompting hypothesis that an HPV-encoded protein inactivates and activates effector yes-associated (YAP1). The HPV E7 oncoprotein is required for HPV-mediated oncogenic transformation. We investigated effects oncoproteins on YAP1 found YAP1, promoting nuclear localization basal cells. activation by binds degrades tumor suppressor tyrosine phosphatase non-receptor type 14 (PTPN14). transcriptional activity extend lifespan primary keratinocytes, indicating contributes carcinogenic activity. Maintaining critical persistence, here we demonstrate expressing be retained compartment epithelia. propose resulting from PTPN14 inactivation essential, targetable relevant carcinogenesis.

Language: Английский

Citations

39
Effect of microtopography on osseointegration of implantable biomaterials and its modification strategies DOI Creative Commons
Yingying Zhang, Zhenmin Fan,

Yanghui Xing

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Sept. 26, 2022

Orthopedic implants are widely used for the treatment of bone defects caused by injury, infection, tumor and congenital diseases. However, poor osseointegration implant failures still occur frequently due to lack direct contact between bone. In order improve biointegration with host bone, surface modification is particular interest requirement in development materials. Implant surfaces that mimic inherent roughness hydrophilicity native have been shown provide osteogenic cells topographic cues promote tissue regeneration new formation. A growing number studies cell attachment, proliferation differentiation sensitive these microtopography. This review a summary latest science modified implants, focusing on how microtopography modulates osteoblast vitro vivo , signaling pathways process types modifications. The aim systematically comprehensive reference information better fabrication orthopedic implants.

Language: Английский

Citations

31
Soft substrates direct stem cell differentiation into the chondrogenic lineage without the use of growth factors DOI Creative Commons
Tosca Roncada, Roxane Bonithon, Gordon Blunn

et al.

Journal of Tissue Engineering, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 1, 2022

Mesenchymal stem cells (MSCs) hold great promise for the treatment of cartilage related injuries. However, selectively promoting cell differentiation in vivo is still challenging. Chondrogenic MSCs usually requires use growth factors that lead to overexpression hypertrophic markers. In this study, first time effect stiffness on MSC has been tested without factors. Three-dimensional collagen and alginate scaffolds were developed characterised. Stiffness significantly affected gene expression ECM deposition. While, all hydrogels supported chondrogenic allowed deposition type II aggrecan, 5.75 kPa hydrogel showed limited production I compared other two formulations. These findings demonstrated can guide within a tissue engineering scaffold suitable defects.

Language: Английский

Citations

31