Spatial biology of cancer evolution

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(5), P. 295 - 313

Published: Dec. 9, 2022

Language: Английский

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Endothelial Dysfunction in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2909 - 2909

Published: Feb. 2, 2023

The cerebral vascular system stringently regulates blood flow (CBF). components of the blood–brain barrier (BBB) protect brain from pathogenic infections and harmful substances, efflux waste, exchange substances; however, diseases develop in cases vessel injuries BBB dysregulation. Vascular pathology is concurrent with mechanisms underlying aging, Alzheimer’s disease (AD), dementia (VaD), which suggests its involvement these mechanisms. Therefore, present study, we reviewed role dysfunction aging neurodegenerative diseases, particularly AD VaD. During development aforementioned changes occur morphology local cells, which, turn, alter CBF, fluid dynamics, integrity. Chronic inflammation dysregulation further exacerbate dysfunction. Multitudinous processes affect cerebrovascular system, whose causes cognitive impairment. Knowledge regarding pathophysiology molecular may lead to discovery clinically relevant biomarkers, facilitate imaging for prevention treatment.

Language: Английский

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The Role of Fibroblasts in Skin Homeostasis and Repair

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1586 - 1586

Published: July 17, 2024

Fibroblasts are typical mesenchymal cells widely distributed throughout the human body where they (1) synthesise and maintain extracellular matrix, ensuring structural role of soft connective tissues; (2) secrete cytokines growth factors; (3) communicate with each other cell types, acting as signalling source for stem niches; (4) involved in tissue remodelling, wound healing, fibrosis, cancer. This review focuses on developmental heterogeneity dermal fibroblasts, their ability to sense changes biomechanical properties surrounding aging, skin repair, pathologic conditions tumour development. Moreover, we describe use fibroblasts different models (e.g., vivo animal vitro systems from 2D 6D cultures) bioengineering informative potential high-throughput assays study under disease contexts personalized healthcare regenerative medicine applications.

Language: Английский

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Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 9, 2025

Abstract Research into cancer treatment has been mainly focused on developing therapies to directly target cells. Over the past decade, extensive studies have revealed critical roles of tumour microenvironment (TME) in initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) emerged as one primary contributors shaping TME, creating a favourable environment for development. Many preclinical identified promising targets CAFs, demonstrating remarkable efficacy some CAF-targeted treatments models. Encouraged by these compelling findings, therapeutic strategies now advanced clinical evaluation. We aim provide comprehensive review relevant subjects including CAF-related markers targets, their multifaceted roles, current landscape ongoing trials. This knowledge can guide future research CAFs advocate investigations targeting CAFs.

Language: Английский

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Heterogeneity of the NIH3T3 Fibroblast Cell Line

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2677 - 2677

Published: Aug. 28, 2022

The embryonic mouse fibroblast cell line NIH3T3 is widely used in life science research, including the study of cycle control and primary cilia. Fibroblasts are most important type connective tissue, as they produce components extracellular matrix determine tissue architecture. However, very heterogeneous consist subtypes specific to their organ residence, among others. was derived from whole embryos that developed pre-birth therefore likely composed different subtypes. Furthermore, prolonged proliferation may have influenced cellular composition. A population unsuitable for any sophisticated research project. We found proportion ciliated cells total highly variable asked whether this a consequence heterogeneity what molecular signatures were associated with it. established sub-cell lines by clonal expansion single characterized them morphologically molecularly. Eventually, myofibroblast-like fibroblast-like generated differ ciliation proliferation. These homogeneous valuable more detailed signatures, not least uncover further pathways contribute formation cilium.

Language: Английский

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The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13511 - 13511

Published: Aug. 31, 2023

Mesenchymal stem/stromal cells (MSCs) are multipotent involved in numerous physiological events, including organogenesis, the maintenance of tissue homeostasis, regeneration, or repair. MSCs increasingly recognized as playing a major, dual, and complex role cancer pathophysiology through their ability to limit promote tumor progression. Indeed, these known interact with microenvironment, modulate behavior cells, influence functions, distant metastasis formation secretion mediators, regulation cell–cell interactions, modulation immune response. This dynamic network can lead establishment immunoprivileged niches new tumors proliferation/differentiation into cancer-associated fibroblasts well stem cells. However, exhibit also therapeutic effects anti-tumor, anti-proliferative, anti-inflammatory, anti-oxidative effects. The interest is currently growing, mainly due selectively migrate penetrate sites, which would make them relevant vectors for advanced therapies. Therefore, this review aims provide an overview double-edged sword implications processes. potential will be reviewed melanoma lung cancers.

Language: Английский

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Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(17)

Published: Aug. 31, 2023

In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes these populations vary depending on their spatial distribution within the tissue immunopathologic cues contributing to progression. addition roles structurally supporting organs remodeling tissue, mediate critical interactions immune cells. These have important implications for defining mechanisms identifying potential therapeutic targets. respiratory tract, particular, determine severity outcome numerous acute chronic lung diseases, including asthma, obstructive pulmonary disease, distress syndrome, idiopathic fibrosis. Here, we review studies spatiotemporal identity lung-derived by which regulate responses insult exposures highlight past, current, future targets relevance fibroblast biology context human diseases. This perspective highlights importance fibroblast-immune crosstalk paves way approaches benefit patients disorders.

Language: Английский

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Fibroblasts in Diabetic Foot Ulcers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2172 - 2172

Published: Feb. 11, 2024

Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These were previously considered to be “passive cells”, solely responsible for ensuring turnover extracellular matrix (ECM). However, their versatility, including ability switch phenotypes response tissue injury and dynamic activity maintenance specific homeostasis integrity have been recently revealed by innovation technological tools such as genetically modified mouse models single cell analysis. highly plastic heterogeneous equipped with multifaceted functions regulation angiogenesis, inflammation well innate stemness characteristics, play a central role delicately regulated process wound healing. Fibroblast dysregulation underlies many chronic conditions, cardiovascular diseases, cancer, inflammatory diabetes mellitus (DM), which represent current major causes morbidity mortality worldwide. Diabetic foot ulcer (DFU), one most severe complications DM affects 40 60 million people. Chronic non-healing DFU wounds expose patients substantial sequelae infections, gangrene, amputation, death. A complete understanding pathophysiology targeting pathways involved fibroblasts required development innovative new therapeutic treatments, critically needed these patients.

Language: Английский

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Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(10), P. 1943 - 1958

Published: Aug. 23, 2024

The drivers of immune evasion are not entirely clear, limiting the success cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate in high-grade serous tubo-ovarian cancer. To this end, first mapped organization by profiling more than 2.5 million cells situ 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics is predictive T natural killer infiltration levels response checkpoint blockade. We then performed Perturb-seq screens identified genetic perturbations—including knockout PTPN1 ACTR8—that trigger state. Finally, show these perturbations, as well PTPN1/PTPN2 inhibitor, sensitize ovarian cytotoxicity, predicted. study thus identifies ways target linking variation, cell-state regulators biology. authors provide resource for combining transcriptomics, genomics, CRISPR silico methods focus on their role evasion.

Language: Английский

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Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(2), P. 616 - 645

Published: Jan. 19, 2024

Abstract Vascular remodeling is the process of structural alteration and cell rearrangement blood vessels in response to injury cause many world’s most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on effects vascular endothelial cells smooth muscle (SMCs) during remodeling, but pericytes, an indispensable population residing largely capillaries, are ignored this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression increased lung tissues PAH patients, HIF2α overexpressed pericytes result greater contractility impaired endothelial-pericyte interaction. Using single-cell RNAseq hypoxia-induced (PH) models, show a major molecular regulator for transformation into SMC-like cells. Pericyte-selective overexpression mice exacerbates PH right ventricular hypertrophy. Temporal cellular lineage tracing shows overexpressing reporter NG2+ (pericyte-selective) relocate from capillaries arterioles co-express SMA. This novel insight crucial role via signaling suggests potential drug target PH.

Language: Английский

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