Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 29, 2023

Endothelial cells line all blood vessels, where they coordinate vessel formation and the blood-tissue barrier via regulation of cell-cell junctions. The nucleus also regulates endothelial cell behaviors, but it is unclear how contributes to activities at periphery. Here, we show that nuclear-localized li nker n ucleoskeleton c ytoskeleton (LINC) complex protein SUN1 vascular sprouting junction morphology function. Loss murine Sun1 impaired destabilized junctions, angiogenic sprouts formed retracted in SUN1-depleted sprouts, zebrafish vessels lacking Sun1b had aberrant junctions defective connections. At cellular level, stabilized promoted function, regulated contractility. Mechanistically, depletion altered behaviors cytoskeleton without changing transcriptional profiles. Reduced peripheral microtubule density, fewer contacts, increased catastrophes accompanied loss, depolymerization phenocopied effects on Depletion GEF-H1, a microtubule-regulated Rho activator, or LINC nesprin-1 rescued cells. Thus, from complex-based interactions affect dynamics Rho-regulated contractility, this long-range important for proper integrity.

Language: Английский

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IGF2BPs as novel m6A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(2), P. 890 - 920

Published: July 20, 2023

m6A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role cancer progression by regulating biological functions. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP) are newly identified 'readers'. They belong to family RNA-binding proteins, which bind sites on different RNA sequences stabilize them promote progression. In this review, we summarize mechanisms upstream factors regulate IGF2BP cancer. The current literature analyzed here reveals that cell proliferation, survival, chemoresistance, inhibit apoptosis, also associated with glycolysis, angiogenesis, immune response tumor microenvironment. Therefore, discovery their as 'readers' characteristic re-expression IGF2BPs cancers, it important elucidate mechanism action immunosuppressive We describe detail regulatory interaction network downstream target RNAs discuss potential clinical applications diagnostic prognostic markers, well recent advances biology therapeutic value.

Language: Английский

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Single-cell analysis of the amphioxus hepatic caecum and vertebrate liver reveals genetic mechanisms of vertebrate liver evolution

Nature Ecology & Evolution, Journal Year: 2024, Volume and Issue: 8(10), P. 1972 - 1990

Published: Aug. 16, 2024

Language: Английский

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The Biology of Vasopressin

Biomedicines, Journal Year: 2021, Volume and Issue: 9(1), P. 89 - 89

Published: Jan. 18, 2021

Vasopressins are evolutionarily conserved peptide hormones. Mammalian vasopressin functions systemically as an antidiuretic and regulator of blood cardiac flow essential for adapting to terrestrial environments. Moreover, acts centrally a neurohormone involved in social parental behavior stress response. Vasopressin synthesis several cell types, storage intracellular vesicles, release response physiological stimuli highly regulated mediated by three distinct G protein coupled receptors. Other receptors may bind or cross-bind vasopressin. is spatially temporally through transcriptional post-transcriptional mechanisms, sex, tissue, cell-specific receptor expression. Anomalies signaling have been observed polycystic kidney disease, chronic heart failure, neuropsychiatric conditions. Growing knowledge the central biological roles has enabled pharmacological advances treat these conditions targeting defective systemic pathways utilizing specific agonists antagonists.

Language: Английский

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Integrating Multi-Omics Analysis for Enhanced Diagnosis and Treatment of Glioblastoma: A Comprehensive Data-Driven Approach

Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3158 - 3158

Published: June 12, 2023

The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There a high relapse rate among patients with GBM despite maximally safe surgery, radiation therapy, temozolomide (TMZ), and treatment. Hence, there an urgent unmet clinical need for new approaches to managing GBM. current study identified modules (MYC, EGFR, PIK3CA, SUZ12, SPRK2) involved disease through the NeDRex plugin. Furthermore, hub genes were comprehensive interaction network containing 7560 proteins related 3860 associated signaling pathways By integrating results of analyses mentioned above again performing centrality analysis, eleven key identified. ProteomicsDB Gliovis databases used determining gene expression normal tissue. NetworkAnalyst mGWAS-Explorer tools miRNAs, SNPs, metabolites these 11 genes. Moreover, literature review recent studies revealed other lists disease. enrichment analysis genes, was performed using ExpressAnalyst, miEAA, MetaboAnalyst tools. Further investigation metabolite roles pathway, joint analyses. this allowed us identify (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, hsa-let-7b-5p), six (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose, X2. piperidinone) 15 distinct that play indispensable role development. top signatures can be targeted establish early diagnostic methods plan personalized treatment strategies.

Language: Английский

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Enhancing immune responses of ESC-based TAA cancer vaccines with a novel OMV delivery system

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 3, 2024

Abstract Embryonic stem cell (ESC)-derived epitopes can act as therapeutic tumor vaccines against different types of tumors Jin (Adv Healthc Mater 2023). However, these have poor immunogenicity and stimulate insufficient CD8 + T responses, which motivated us to develop a new method deliver enhance their effectiveness. Bacterial outer membrane vesicles (OMVs) serve immunoadjuvants delivery vector for antigens. In the current study, we engineered OMV platform co-delivery ESC-derived antigens immune checkpoint inhibitors (PD-L1 antibody). An Staphylococcal Protein A (SpA) was created non-specifically bind anti-PD-L1 antibody. SpyCatcher (SpC) SpA were fused into protein OmpA capture SpyTag-attached peptides PD-L1 antibody, respectively. The modified able efficiently conjugate with TAAs antibody (SpC-OMVs SpT-peptides anti-PD-L1), increasing residence time in body. results showed that combination therapy ESC-based delivered by had significant inhibitory effects mouse model. Specifically, it effective reducing growth enhancing IFN-γ-CD8 responses number memory cells antigen-specific cells. Overall, system is versatile TAA cancer vaccines. Graphical

Language: Английский

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An evolutionary timeline of the oxytocin signaling pathway

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 17, 2024

Abstract Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of entire signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, phylostratigraphy, we assigned genes supporting different phylostrata based on when found they likely arose evolution. We show that majority (64%) are ‘modern’. Most modern evolved around emergence vertebrates or jawed (540 - 530 million years ago, ‘mya’), including OXTR , OXT CD38 . Of those, 45% were under positive selection at some point during vertebrate also 18% ‘ancient’, meaning their dates back cellular organisms opisthokonta (3500–1100 mya). The remaining (18%) after ancient before classified as ‘medium-aged’. Functional analyses revealed that, humans, medium-aged highly expressed contractile organs, while primarily brain muscle tissue.

Language: Английский

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ECO: the Evidence and Conclusion Ontology, an update for 2022

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D1515 - D1521

Published: Oct. 19, 2021

Abstract The Evidence and Conclusion Ontology (ECO) is a community resource that provides an ontology of terms used to capture the type evidence supports biomedical annotations assertions. Consistent information with ECO allows tracking annotation provenance, establishment quality control measures, evidence-based data mining. in use by dozens repositories resources both specific general areas focus. continually being expanded enhanced response user requests as well our aim adhere best-practices for development. support team engages multiple collaborations other ontologies annotating groups. Here we report on recent updates itself associated are available through this project. project products freely download from website (https://evidenceontology.org/) GitHub (https://github.com/evidenceontology/evidenceontology). released into public domain under CC0 1.0 Universal license.

Language: Английский

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Convergent evolution of venom gland transcriptomes across Metazoa

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 119(1)

Published: Dec. 30, 2021

Significance On more than 100 occasions, animals have independently evolved the ability to produce and deliver potent secretions subdue prey or predators—venom. This prompts following question: Have repeatedly adopted same genetic toolkit for venom production? In this study, we found, surprisingly, that glands of different animal lineages had similar global gene expression patterns. Notably, groups genes involved in protein secretion, especially stress response pathways, levels, revealing many come up with solution independently. other hand, signaling regulatory networks lineage-specific patterns, suggesting way which cells are regulated communicate might reflect diverse developmental origins systems.

Language: Английский

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Parallel evolution of amphioxus and vertebrate small-scale gene duplications

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: Nov. 18, 2022

Abstract Background Amphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan genome organization with vertebrates but lack their 2R whole-genome duplications developmental complexity. For these reasons, amphioxus frequently used as an outgroup to study vertebrate evolution Evo-Devo. Aside from duplications, genes continuously duplicate on smaller scale. Small-scale duplicated can be found in both genomes, while only genomes have product of duplications. Here, we explore history small-scale gene lineage compare it small- large-scale duplication vertebrates. Results We present European ( Branchiostoma lanceolatum ) thanks new, high-quality reference. find that, despite its overall evolution, has had similar one observed parallel profiles between conserved functional constraints duplication. Moreover, duplicates show levels expression patterns specialization ones genes. also strong conservation synteny two distant species, B. floridae , major chromosomal rearrangements. Conclusions In contrast slower amphioxus’ resembles that quantitative terms.

Language: Английский

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