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

Yap and Taz promote osteogenesis and prevent chondrogenesis in neural crest cells in vitro and in vivo DOI
Xiaolei Zhao,

Li Tang,

Tram P. Le

et al.

Science Signaling, Journal Year: 2022, Volume and Issue: 15(757)

Published: Oct. 25, 2022

Neural crest cells (NCCs) are multipotent stem that can differentiate into multiple cell types, including the osteoblasts and chondrocytes, constitute most of craniofacial skeleton. Here, we show through in vitro vivo studies transcriptional regulators Yap Taz have redundant functions as key determinants specification differentiation NCCs or chondrocytes. Primary cultured deficient

Language: Английский

Citations

30
Isoform-resolved transcriptome of the human preimplantation embryo DOI Creative Commons
Denis Torre, Nancy Francoeur, Yael Kalma

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 30, 2023

Abstract Human preimplantation development involves extensive remodeling of RNA expression and splicing. However, its transcriptome has been compiled using short-read sequencing data, which fails to capture most full-length mRNAs. Here, we generate an isoform-resolved early human by performing long- on 73 embryos spanning the zygote blastocyst stages. We identify 110,212 unannotated isoforms transcribed from known genes, including highly conserved protein-coding loci key developmental regulators. further 17,964 5,239 are largely non-coding, primate-specific, associated with transposable elements. These widely supported integration published multi-omics datasets, single-cell 8CLC blastoid studies. Alternative splicing gene co-expression network analyses reveal that embryonic genome activation is disruption transient upregulation modules. Together, these findings show embryo far more complex than currently known, will act as a valuable resource empower future studies exploring development.

Language: Английский

Citations

18
Hierarchically Biomimetic Scaffolds with Anisotropic Micropores and Nanotopological Patterns to Promote Bone Regeneration via Geometric Modulation DOI
Xin Wei, Jiaxin Chen,

Hui‐Yuan Shen

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(17)

Published: March 16, 2024

Structural engineering is an appealing means to modulate osteogenesis without the intervention of exogenous cells or therapeutic agents. In this work, a novel 3D scaffold with anisotropic micropores and nanotopographical patterns developed. Scaffolds oriented pores are fabricated via selective extraction water-soluble polyethylene oxide from its poly(ε-caprolactone) co-continuous mixture uniaxial stretching. The plate apatite-like lamellae subsequently hatched on pore walls through surface-induced epitaxial crystallization. Such unique geometric architecture yields synergistic effect osteogenic capability. prepared leads 19.2% 128.0% increase in alkaline phosphatase activity rat bone mesenchymal stem compared that scaffolds only patterns, respectively. It also induces greatest upregulation osteogenic-related gene expression vitro. cranial defect repair results demonstrate effectively promotes new regeneration, as indicated by 350% collagen I vivo isotropic porous surface nanotopology after implantation for 14 weeks. Overall, work provides motifs transduction biophysical cues scaffolds, which promising option tissue applications.

Language: Английский

Citations

8
Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis DOI Creative Commons
Ahmed Raslan,

Tho X. Pham,

Jisu Lee

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 27, 2024

Abstract Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into alterations in we performed single RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated states enriched for hypoxia, glycolysis YAP/TAZ activity ACKR1+ venous TrkB+ capillary cells. Endothelial activation prevalent mice can also be detected human fibrotic lungs. Longitudinal combined lineage tracing demonstrate that resolves mouse but persists ones, indicating a failure the vasculature to return quiescence. Genes cells vivo induced vitro by activating YAP/TAZ. cooperate BDNF, TrkB ligand reduced lungs, promote morphogenesis. These findings offer insights dysfunction may contribute defective injury repair persistent fibrosis.

Language: Английский

Citations

7
Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway DOI Creative Commons
Marcella La Noce, Antonietta Stellavato, Valentina Vassallo

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2899 - 2899

Published: Oct. 26, 2021

Background: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation hDPSCs (human dental pulp stem cells) three hyaluronans forms: linear pharmaceutical-grade at high (HHA) low (LHA) hybrid cooperative complexes (HCC), containing both sizes. Methods: were treated HHA, LHA, HCC for 7, 14 21 days. The effects on evaluated by qRT-PCR WB markers Alizarin Red S staining. To identify involved pathway, CD44 was analyzed immunofluorescence, YAP/TAZ expression measured qRT-PCR. Moreover, inhibitor-1 used, loss function qRT-PCR, immunofluorescence. Results: We showed that all improves osteogenesis. Among these, is main inducer osteogenesis, along overexpression bone related upregulating CD44. also found this biological process subordinate activation pathway. Conclusions: HA’s can have a relevant impact HA performance regeneration, unveil new mechanism which acts cells.

Language: Английский

Citations

34
Importance of the Microenvironment and Mechanosensing in Adipose Tissue Biology DOI Creative Commons
Simon Lecoutre, Mélanie Lambert, Krzysztof Drygalski

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2310 - 2310

Published: July 27, 2022

The expansion of adipose tissue is an adaptive mechanism that increases nutrient buffering capacity in response to overall positive energy balance. Over the course expansion, microenvironment undergoes continual remodeling maintain its structural and functional integrity. However, long run, remodeling, typically characterized by adipocyte hypertrophy, immune cells infiltration, fibrosis changes vascular architecture, generates mechanical stress on cells. This stimulus then transduced into a biochemical signal alters function through mechanotransduction. In this review, we describe physical occurring during how they regulate cell physiology promote obesity-associated dysfunction tissue.

Language: Английский

Citations

28
Adipogenesis or osteogenesis: destiny decision made by mechanical properties of biomaterials DOI Creative Commons
Ting Su, Mimi Xu, Feng Lu

et al.

RSC Advances, Journal Year: 2022, Volume and Issue: 12(38), P. 24501 - 24510

Published: Jan. 1, 2022

Regenerative medicine affords an effective approach for restoring defect-associated diseases, and biomaterials play a pivotal role as cell niches to support the behavior decide destiny of differentiation. Except chemical inducers, mechanical properties such stiffness, pore size topography crucial in regulation behaviors functions. Stiffness may determine adipogenesis or osteogenesis mesenchymal stem cells (MSCs)

Language: Английский

Citations

27
Highly Elastic and Anisotropic Wood‐Derived Composite Scaffold with Antibacterial and Angiogenic Activities for Bone Repair DOI
Jiaqing Chen,

Xiangheng He,

Tianyi Sun

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(21)

Published: April 26, 2023

Scaffold-based tissue engineering is a promising strategy to address the rapidly growing demand for bone implants, but developing scaffolds with extracellular matrix-like structures, suitable mechanical properties, and multiple biological activities remains huge challenge. Here, it aimed develop wood-derived composite scaffold an anisotropic porous structure, high elasticity, good antibacterial, osteogenic, angiogenic activities. First, natural wood treated alkaline solution obtain oriented cellulose skeleton which can not only simulate collagen fiber in also greatly improve convenience of clinical implantation. Subsequently, chitosan quaternary ammonium salt (CQS) dimethyloxalylglycine (DMOG) are further modified on elastic through polydopamine layer. Among them, CQS endows antibacterial activity, while DMOG significantly improves scaffold's osteogenic Interestingly, characteristics synergistically enhance expression yes-associated protein/transcriptional co-activator PDZ binding motif signaling pathway, thereby effectively promoting differentiation. Therefore, this expected have potential application treatment defects.

Language: Английский

Citations

15
Hippo cell signaling and HS-proteoglycans regulate tissue form and function, age-dependent maturation, extracellular matrix remodeling, and repair DOI
James Melrose

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(3), P. C810 - C828

Published: Jan. 15, 2024

This review examined how Hippo cell signaling and heparan sulfate (HS)-proteoglycans (HSPGs) regulate tissue form function. Despite being a nonweight-bearing tissue, the brain is regulated by mechanoresponsive pathways during embryonic development. HS-proteoglycans interact with growth factors, morphogens, extracellular matrix components to development pathology. Pikachurin Eyes shut (Eys) dystroglycan stabilize photoreceptor axoneme primary cilium ribbon synapse facilitating phototransduction neurotransduction bipolar retinal neuronal networks in ocular vision, human sense. Another HSPG, Neurexin interacts structural adaptor proteins synapses ensure specificity of neural interactions, aids synaptic potentiation plasticity neurotransduction. HSPGs also blood-brain barrier motor neuron basal structures neuromuscular junction. Agrin perlecan localize acetylcholinesterase its receptors junction essential for control. The mechanosensory hub on neurons, utilized YES associated protein (YAP)-transcriptional coactivator PDZ-binding motif (TAZ) Hippo, Hh, Wnt, transforming factor (TGF)-β/bone (BMP) receptor tyrosine kinase signaling. Members glypican HSPG proteoglycan family Smoothened Patched G-protein coupled Hh Wnt Control glycosyl sulfotransferases endogenous protease expression TAZ YAP represents mechanism whereby fine structure can be potentially modulated spatiotemporally morphogenesis similar manner controls sialyltransferase mediation cell-cell recognition, dysfunctional sialic acid feature many tumors.

Language: Английский

Citations

6
YAP/TAZ as Molecular Targets in Skeletal Muscle Atrophy and Osteoporosis DOI Creative Commons
Youngjoo Kwon

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Skeletal muscles and bones are closely connected anatomically functionally. Age-related degeneration in these tissues is associated with physical disability the elderly significantly impacts their quality of life. Understanding mechanisms age-related musculoskeletal tissue crucial for identifying molecular targets therapeutic interventions skeletal muscle atrophy osteoporosis. The Hippo pathway a recently identified signaling that plays critical roles development, homeostasis, regeneration. Yes-associated protein (YAP) transcriptional coactivator PDZ-binding motif (TAZ) key downstream effectors mammalian pathway. This review highlights fundamental YAP TAZ homeostatic maintenance regeneration bones. YAP/TAZ play significant role stem cell function by relaying various environmental signals to cells. osteoporosis related dysfunction or senescence triggered dysregulation resulting from reduced mechanosensing mitochondrial In contrast, activation can suppress may be used as basis development potential strategies. Thus, targeting holds alleviating bone improving life elderly.

Language: Английский

Citations

5