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Single-Cell Transcriptomic Analysis of Tumor Heterogeneity and the Microenvironment in Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is characterized by progressive mucus accumulation, extensive stromal fibrosis, rare extraperitoneal metastasis … lic activity and identified a candidate pro-angiogenic network involving POSTN+ fibroblasts, RSPO3+ pericytes, and endothelial cells, potentially mediated by VEGFA-VEGFR2 signaling. Retrospective observations from three recurrent PMP cases further suggested the potential therapeutic value of VEGFR2-targeted anti-angiogenic therapy. Overall, this study provi …

Ageing of the skeletal muscle as a barrier to cell therapy: Cell sources, microenvironmental failure and autologous alternatives.

The progressive decline of skeletal muscle (SkM) regeneration is a central feature of ageing. In sarcopenia, the age-related loss of muscle … uding age-related sarcopenia, encompassing satellite cells (SCs), mesenchymal stromal cells (MSCs), pericytes (PCs)/mesoangioblasts, and hematopoietic stem cells (HSCs), and delineates how each population declines with age. A particular focus is placed on breakthroughs in aged-niche conditioning and autologous cell therapy via pluripotent stem cell (PSC) di …

Experimental model systems to study vascular aging.

Vascular aging contributes to systemic dysfunction and underlies many age-related diseases, driven by structural and functional changes across various cell types, including endothelial cells, vascular smooth muscle cells, pericytes, and cardiomyocytes. This review highlights experimental models that facilitate mechanistic insights and the development of novel therapeutic approaches for vascular aging, emphasizing both in vitro and in vivo methodologies. This review discusses in vitro models utilizing primary and induced pluripotent stem cell (iPSC)-derived cultures across two-dimensional (2D) …

A novel peptide blocking CD93/IGFBP7 interaction normalizes tumor vessels and synergizes with radiotherapy for cancer immunotherapy.

The aberrant tumor vasculature fosters a permissive microenvironment that impedes immune effector cell infiltration and simultaneously promo … c CD8+ T cells and NK cells infiltration through enhanced blood perfusion and increased coverage of pericytes and vascular smooth muscle cells. More importantly, CBP-D8 peptide combined with radiotherapy significantly abrogated tumor growth and elicited systemic antitumor immune response. Our study identified a novel peptide blocking CD93/IGFBP7 interaction …

Stromal ARHGEF15 Correlates With Inflammatory EMT and Stromal-Immune Crosstalk During Inflammatory Bowel Disease-To-Colorectal Cancer Progression.

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC), but how chronic intestinal inflammation dr … IBD-to-cancer continuum. ARHGEF15 emerged as a stromal gene enriched in CD74hi HLA-DRB1hi arterial pericytes within inflamed tissue. Its expression rose steadily from IBD to CRC and tracked with epithelial-mesenchymal transition (EMT) activity. In CRC, higher ARHGEF15 expression was associated with shorter overall and progression-free survival. These retro …

Divergent stem cell mechanisms govern the primary body axis and appendage regeneration in the axolotl.

Exploring the fundamental mechanisms of organ regeneration is crucial for advancing regenerative medicine. The axolotl tail represents an opportunity to study regeneration of the primary axis including segmented muscle, vertebrae, and skin. During tail development, muscle stem cells (MuSCs) displayed expected specificity to the muscle lineage. Tail amputation, however, induced expansion of MuSC potential yielding clonal contribution to muscle, connective tissue including cartilage, pericytes, and fibroblasts. This expanded potential was not observed during limb regeneration, and cross-transpla…

CD38 Inhibition Ameliorates Age-Related CognitiveDecline via a Choroid Plexus-Cerebrospinal Fluid-Hippocampus Axis.

Age-related cognitive decline represents a major and unresolved challenge of human aging. Here, we identify the NAD+-consuming enzyme CD38 as a central regulator of cognitive aging acting through a choroid plexus-cerebrospinal fluid (CSF)-hippocampus axis. CD38 expression increases with age and localizes primarily to pericytes in the choroid plexus, where it depletes NAD+, impairs mitochondrial function, and promotes cellular senescence. Genetic ablation or pharmacological inhibition of CD38 restores NAD+ levels, suppresses senescence markers, and improves choroid plexus function, resulting in…

Retinal Astrocytes: Key Coordinators of Developmental Angiogenesis and Neurovascular Homeostasis in Health and Disease.

Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. … at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization mi …

Dietary Lipids and Lipid-Mediated Signaling Neurovascular Unit Dysfunction: Implications for Alzheimer's and Parkinson's Diseases Pathogenesis.

Dysregulated lipid homeostasis is closely related to the occurrence and development of various neurological diseases, with the principal mechanism being the damage to the neurovascular unit (NVU). The NVU consists of neurons, vascular endothelial cells, pericytes, astrocytes, and microglia, which integrates glial-vascular-neuronal tripartite communication through tight junction-regulated molecular trafficking. The tripartite communication among these components is essential for cerebrovascular hemodynamic homeostasis and neural signal transmission. Abnormal lipid-mediated signaling impairs the…

Dynamics of bleomycin-induced lung injury at single-nucleus resolution.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for studying individual cell populations in complex tissues during inj … lations during injury. Additionally, we identified sizeable populations of rare cell types, such as pericytes, and cells sensitive to digestion protocols, including a population of activated fibroblasts. These results indicate that snRNA-seq recapitulates the dynamic changes associated with injury as previously reported using single-cell methods and outperf …

Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.

Hepatic stellate cells (HSCs) play a crucial role in the pathogenesis of liver fibrosis in metabolic dysfunction-associated steatohepatitis (MASH), a condition characterized by excessive fat accumulation in the hepatocytes, unrelated to alcohol consumption. In a healthy liver, HSCs are quiescent, store vitamin A, and function as pericytes. However, in response to liver injury and inflammation, HSCs become activated. In MASH, HSC activation is driven by metabolic stress, lipotoxicity, and chronic inflammation. Injured hepatocytes, recruited macrophage, capillarized sinusoidal endothelial cells,…

Transgenic mouse models for investigating human DUX4 expression during development and its roles in FSHD pathophysiology.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy caused by aberrant expression of the DUX4 retrogene, and it … reminiscent of mosaic DUX4 expression in FSHD. Within skeletal muscles, DUX4 lineage cells include pericytes, an interstitial cell that contributes to muscle regeneration and repair. Overall, this study introduces a new research tool for the field, and provides new insight into potential developmental mechanisms underlying FSHD pathophysiology.

Transferrin-Functionalized Liposomes Enhance MAPT-ASO Transport Across a 3D Blood-Brain Barrier Microvascular Network Model.

Tau pathology is a defining hallmark of Alzheimer's disease (AD), closely associated with cognitive decline. Antisense oligonucleotides targeting the tau-encoding gene MAPT (MAPT-ASO) have shown promise in clinical trials, but their therapeutic potential is limited by poor delivery across the blood-brain barrier (BBB). In this study, we developed transferrin (TF)-functionalized liposomes encapsulating MAPT-ASOs and evaluated their transport across a 3D self-assembled microvascular BBB model composed of human brain microvascular endothelial cells, astrocytes, and pericytes embedded in a fibrin …

Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.

Cerebral malaria is a severe neurovascular complication of Plasmodium falciparum infection, with high mortality rates even after treatment with effective antimalarials. Limitations in current experimental models have hindered our knowledge of the disease. We developed a 3D blood-brain barrier (BBB) model with enhanced barrier properties using primary brain endothelial cells, astrocytes, and pericytes. Exposure to parasite egress products increases microvascular permeability, likely due to transcriptional downregulation of junctional and vascular development genes in endothelial cells. In addit…

GPX1 и RCN1 как новые эндоплазмические ретикулумные биомаркеры, связанные со стрессом, в многоклерозном мозге и их участие в APP-CD74 Pathway: A Integrated Study Commining Machine Learning и Multi-Omics.

В ходе этого исследования были выявлены 13 связанных с эндоплазмическим ретикулумным стрессом (ERS) биомаркеров, связанных с множественным склерозом (MS), на основе комплексного анализа биоинформатики (включая анализ взвешенной генной сети совместного самовыражения и алгоритмы машинного обучения) и секвенирования в одной клетке в сочетании с проверкой в экспериментальной модели мыши аутоиммунной энцефаломиелита (EAE). Среди них GPX1, RCN1 и UBE2D3 показали высокое диагностическое значение (AUC > 0,7, p < 0,05), и диагностический потенциал GPX1 и RCN1 был подтвержден в модели животных. Исследов

Совпадение в аннотации оригинала
This study identified 13 endoplasmic reticulum stress (ERS)-related biomarkers associated with multiple sclerosis (MS) through integrated bi … lated genes divided MS patients into two subtypes. Single-cell sequencing showed that microglia and pericytes were the cell types with the highest expression of key ERS-related genes, and the APP-CD74 pathway was enhanced in the brain tissue of MS patients. Mendelian randomization analysis suggested that GPX1 plays a protective role in MS. These findings re …

Regulation of intestinal epithelial homeostasis by mesenchymal cells.

The gastrointestinal tract harbors diverse microorganisms in the lumen. Epithelial cells segregate the luminal microorganisms from immune cells in the lamina propria by constructing chemical and physical barriers through the production of various factors to prevent excessive immune responses against microbes. Therefore, perturbations of epithelial integrity are linked to the development of gastrointestinal disorders. Several mesenchymal stromal cell populations, including fibroblasts, myofibroblasts, pericytes, and myocytes, contribute to the establishment and maintenance of epithelial homeost…

Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.

Cerebral small vessel disease (cSVD) encompasses a heterogeneous group of age-related small vessel pathologies that affect multiple regions. … function is rightly considered a central feature of cSVD, the contributions of smooth muscle cells, pericytes, and other perivascular cells warrant continued investigation.

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized … ellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim …

The neurovasculature as a target in temporal lobe epilepsy.

The blood-brain barrier (BBB) is a physiological barrier maintaining a specialized brain micromilieu that is necessary for proper neuronal function. Endothelial tight junctions and specific transcellular/efflux transport systems provide a protective barrier against toxins, pathogens, and immune cells. The barrier function is critically supported by other cell types of the neurovascular unit, including pericytes, astrocytes, microglia, and interneurons. The dysfunctionality of the BBB is a hallmark of neurological diseases, such as ischemia, brain tumors, neurodegenerative diseases, infections,…

Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies.

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells' (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo-derived senescence signature (SenSig) using a foreign body response-driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and "cartilage-like" fibroblasts as senescent and defined cell type-specific senescence-associated secretory phenotypes (SASPs). Transfer learning an…