Search Results (1,726)

The extracellular matrix (ECM) supports spermatogonial stem cell (SSC) function by mimicking biochemical and structural features of the native niche. However, optimal feeder systems and ECM materials remain key limitations in porcine SSC (pSSC) cultures. We developed a porcine-derived ECM (pECM) from porcine feet and evaluated its effectiveness in supporting pSSC maintenance and proliferation under feeder-dependent conditions. We examined protein molecular weight distribution and pECM extract composition. Surface characterization was performed using scanning electron microscopy and atomic force microscopy. We compared pECM with conventional coatings, including gelatin and non-coated controls, using morphological analysis, WST-1 assay, cell cycle analysis, and gene/protein expression of SSC markers. pECM promoted larger, well-defined pSSC colonies and enhanced stemness-related marker expression, including PGP9.5, Thy-1, PLZF, GFRA1, NANOG, and VASA. Additionally, pECM facilitated active pSSC proliferation while suppressing feeder overgrowth, contributing to a stable and functional co-culture environment. Conversely, gelatin supported early feeder proliferation but led to growth saturation, whereas N/C showed delayed attachment and reduced viability. These findings suggest that pECM mimics the native SSC niche and improves pSSC culture. The dual function of pECM in regulating feeder behavior and enhancing pSSC maintenance highlights its potential as a biomaterial for species lacking established feeder-free protocols. Full article

We present a hybrid partial differential equation-agent-based model (PDE-ABM). In our framework, tumor cells secrete tumor angiogenic factor (TAF), while endothelial cells chemotactically migrate and branch in response. Reaction–diffusion PDEs for TAF, oxygen, and cytotoxic drug are coupled to discrete stochastic dynamics of tumor cells and endothelial tip cells, ensuring multiscale integration. Motivated by observed perfusion heterogeneity in tumors and its pharmacokinetic consequences, we conduct a linear stability analysis for a reduced endothelial–TAF reaction–diffusion subsystem and derive an explicit finite-domain threshold for Turing instability. We demonstrate that bidirectional coupling, where endothelial cells both chemotactically migrate along TAF gradients and secrete TAF, is necessary and sufficient to generate spatially periodic vascular clusters and inter-cluster hypoxic regions. These emergent patterns produce heterogeneous drug penetration and resistant niches. Our results identify TAF clearance, chemotactic sensitivity, and endothelial motility as effective levers to homogenize perfusion. The model is two-dimensional and employs simplified kinetics, and we outline necessary extensions to three dimensions and saturable kinetics required for quantitative calibration. The study links reaction–diffusion mechanisms with clinical principles and suggests actionable strategies to mitigate resistance by targeting endothelial–TAF feedback. Full article

The Krüppel-like factor (KLF) family of transcription regulators plays pivotal roles in adipogenesis, myogenesis, and metabolism. While comprehensively studied in humans and mice, its characterization in cattle remains limited, especially within the skeletal muscle niche. This study aimed to systematically characterize the KLF family in Bos taurus and elucidate its role in breed-specific muscular development. We employed an integrated approach of comparative genomics and single-nucleus RNA sequencing (snRNA-seq) on longissimus dorsi muscle from Angus (ANG, beef breed) and Holstein (HST, dairy breed) cattle. Phylogenomic analysis identified 14 KLF genes, revealing evolutionary conservation and potential functional divergence. snRNA-seq delineated 11 distinct cell populations and uncovered cell-type-specific expression patterns of KLFs. Further machine learning based analysis pinpointed KLF6, KLF9, KLF10, and KLF12 as key global drivers of transcriptional differences between breeds, while KLF6 was identified as a major cell-type-specific contributor in lymphatic endothelial cells. Our work provides a foundational resource for understanding the KLF family in cattle and identifies promising candidate genes for improving meat production traits through molecular breeding. Full article

In the long-term evolutionary process, species maintain a natural balance within certain limits through communication. As plants grow and function as producers, root enrichment fosters a dynamic rhizosphere microbiome, which serves not only as a disintegrator within the ecological niche but also as a medium for interaction between the host and the soil environment. The life cycle of fungi within the microbiome alternates between single-cell resting spores and multicellular trophic mycelia. This cycle not only establishes a stable rhizosphere environment but also plays a crucial role in regulating both intra- and interspecific information transmission, significantly impacting the environment and plant health. The rhizosphere microbiome, particularly the fungi it contains, can be harnessed to repair environmental damage and either promote the growth of the plant host or inhibit pathogens. However, the mechanisms underlying these actions remain inadequately understood, hindering the advancement of artificial regulation. Additionally, the variability of influencing factors, along with unstable genes and traits, poses challenges to industrial development. In conclusion, this paper focuses on the fungal components of the rhizosphere microbiome, introduces the mechanisms of communication and current applications, and further analyzes existing bottlenecks and potential solutions. The aim is to provide theoretical support for achieving green, sustainable agriculture through biological means. Full article

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidative phosphorylation; the secretion of adipokines such as leptin and IL-6, which promote epithelial-to-mesenchymal transition, invasion, and immune evasion; regulation of osteoclastogenesis via RANKL expression; and the release of extracellular vesicles that reprogram cancer cell metabolism. Clinical and experimental studies show that BMA expansion correlates with increased tumor burden and poorer outcomes in breast, prostate, lung cancers, and multiple myeloma. Additionally, BMAs actively promote therapeutic resistance through metabolic rewiring and drug sequestration. Experimental models, ranging from in vitro co-cultures to in vivo patient-derived xenografts, demonstrate the complex roles of BMAs and also reveal important translational gaps. Despite promising preclinical approaches such as metabolic inhibitors, PPARγ modulation, adipokine blockade, and lifestyle changes, no therapies directly targeting BMAs have yet reached clinical practice. This review compiles current evidence on the biology of BMAs, their tumor-promoting interactions, and potential therapeutic strategies, while also highlighting unresolved questions about BMA heterogeneity, lipid flux, and immunometabolic crosstalk. By revealing how bone marrow adipocytes actively shape the metastatic niche through metabolic, endocrine, and immunological pathways, this review highlights their potential as novel biomarkers and therapeutic targets for improving the management of bone metastases. Full article

Metastases are responsible for the majority of cancer-related deaths and remain one of the most complex and therapeutically challenging hallmarks of cancer. The metastatic cascade involves a multistep process by which cancer cells invade local tissue, enter and survive in circulation, extravasate, and ultimately colonize distant organs. Increasingly, the tumor microenvironment (TME), particularly the extracellular matrix (ECM), has emerged as a central regulator of these steps. Far from being a passive scaffold, the ECM actively influences cancer progression through its biochemical signals, structural properties, and dynamic remodeling. Among ECM components, collagens play a particularly pivotal role by mediating tumor cell adhesion, migration, invasion, survival, immune evasion, and therapeutic resistance. This narrative review synthesizes current knowledge of the dual roles of collagen in the metastatic process, with a focus on the cellular and molecular mechanisms. We highlight how altered ECM architecture and signaling contribute to metastatic niche formation and explore the potential of targeting ECM components as a strategy to enhance cancer therapy and improve patient outcomes. Full article

The endometrium is a highly dynamic tissue central to female reproductive function, undergoing nearly 500 cycles of proliferation, differentiation, shedding, and regeneration throughout a woman’s reproductive life. This remarkable regenerative capacity is driven by a reservoir of endometrial stem/progenitor cells (ESCs), which are crucial for maintaining tissue homeostasis. Dysregulation of these cells is linked to a variety of clinical disorders, including menstrual abnormalities, infertility, recurrent pregnancy loss, and serious gynecological conditions such as endometriosis and endometrial cancer. Recent advancements in organoid technology and lineage-tracing models have provided insights into the complex cellular hierarchy that underlies endometrial regeneration and differentiation. This review highlights the latest breakthroughs in endometrial stem cell biology, focusing particularly on 3D in vitro platforms that replicate endometrial physiology and disease states. By integrating these cutting-edge approaches, we aim to offer new perspectives on the pathogenesis of endometrial disorders and establish a comprehensive framework for developing precision regenerative therapies. Full article

β-thalassemia is a chronic genetic blood disorder characterized by defective β-globin synthesis, requiring frequent transfusions and resulting in iron overload, immune dysfunction, and increased susceptibility to infections. In these immunocompromised patients, altered immune responses lead to significant changes in the human virome, promoting viral persistence, reactivation, and expansion of pathogenic viral communities. This review explores the intricate relationship between β-thalassemia and the human virome, focusing on how clinical interventions and immune abnormalities reshape viral dynamics, persistence, and pathogenicity. Patients with β-thalassemia exhibit profound innate and adaptive immune dysregulation, including neutrophil dysfunction, T cell senescence, impaired B cell and NK cell activity, and expansion of myeloid-derived suppressor cells. These alterations create an immunological niche that favors viral reactivation and virome expansion. Iron overload enhances viral replication, while chronic transfusions introduce transfusion-transmitted viruses. Splenectomy and allo-HSCT further compromise viral surveillance. Additionally, disruptions in the gut virome, particularly bacteriophage-driven dysbiosis, may exacerbate inflammation and impair host–virus homeostasis. The human virome is not a passive bystander but a dynamic player in the pathophysiology of β-thalassemia. Understanding virome–immune interactions may offer novel insights for infection monitoring, risk stratification, and precision therapies in thalassemic patients. Full article

Pulmonary fibrosis (PF) is a progressive and fatal lung disease characterized by irreversible alveolar destruction and pathological extracellular matrix (ECM) deposition. Currently approved agents (pirfenidone and nintedanib) slow functional decline but do not reverse established fibrosis or restore functional alveoli. Multifunctional bioscaffolds present a promising therapeutic strategy through targeted modulation of critical cellular processes, including proliferation, migration, and differentiation. This review synthesizes recent advances in scaffold-based interventions for PF, with a focus on their dual mechano-epigenetic regulatory functions. We delineate how scaffold properties (elastic modulus, stiffness gradients, dynamic mechanical cues) direct cell fate decisions via mechanotransduction pathways, exemplified by focal adhesion–cytoskeleton coupling. Critically, we highlight how pathological mechanical inputs establish and perpetuate self-reinforcing epigenetic barriers to regeneration through aberrant chromatin states. Furthermore, we examine scaffolds as platforms for precision epigenetic drug delivery, particularly controlled release of inhibitors targeting DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) to disrupt this mechano-reinforced barrier. Evidence from PF murine models and ex vivo lung slice cultures demonstrate scaffold-mediated remodeling of the fibrotic niche, with key studies reporting substantial reductions in collagen deposition and significant increases in alveolar epithelial cell markers following intervention. These quantitative outcomes highlight enhanced alveolar epithelial plasticity and upregulating antifibrotic gene networks. Emerging integration of stimuli-responsive biomaterials, CRISPR/dCas9-based epigenetic editors, and AI-driven design to enhance scaffold functionality is discussed. Collectively, multifunctional bioscaffolds hold significant potential for clinical translation by uniquely co-targeting mechanotransduction and epigenetic reprogramming. Future work will need to resolve persistent challenges, including the erasure of pathological mechanical memory and precise spatiotemporal control of epigenetic modifiers in vivo, to unlock their full therapeutic potential. Full article

Glioblastoma (GBM) is an aggressive and lethal malignant brain tumor. Cell–cell interactions (CCIs) in the tumor microenvironment, mediated by ligand–receptor (LR) pairs, are known to contribute to its poor prognosis. However, the prognostic influence of CCIs on patients with GBM and the spatial expression profiles of such LR pairs within tumor tissues remain incompletely understood. This study aimed to identify prognostic LR pairs in GBM and their intratumoral localization via multitranscriptomic analysis. The CCIs among GBM cells as well as between GBM and niche cells were comprehensively evaluated using 40,958 cells in single-cell RNA sequencing datasets. They were found to form intercellular networks in GBM by specific LR pairs, which were mainly implicated in extracellular matrix (ECM)-related biological processes. Survival analysis revealed that 13 LR pairs related to ECM biological processes contributed to poor prognosis (p < 0.05, and 95% confidence intervals > 1). Notably, our spatial transcriptomic analysis using three independent GBM cohorts revealed that the identified poor prognostic LR pairs were localized in specific regions within GBM tissues. Although the clinical importance of these LR pairs requires further investigation, our findings suggest potential therapeutic targets for GBM. Full article

Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to fresh-frozen specimens of one HCC and one liver metastasis (>16,000 genes per sample, >97% mapping rates) as a proof-of-principle two-specimen study, cross-validated in human proteomics and patients’ survival datasets. Transcriptional clustering revealed spatially distinct compartments, rare cell states, and pathway alterations, which were further compared against an independent systemic dataset. Results: HCC displayed an ordered lineage architecture, with transformed hepatocyte-like tumor cells broadly dispersed across the tissue and more differentiated hepatocyte-derived cells restricted to localized zones. By contrast, liver metastases showed two sharply compartmentalized domains: an invasion zone, where proliferative stem-like tumor cells occupied TAM-rich boundaries adjacent to hypoxia-adapted tumor-core cells, and a plasticity zone, which formed a heterogeneous niche of cancer–testis antigen–positive germline-like cells. Across both tumor types, we detected a conserved metabolic program of “porphyrin overdrive,” defined by reduced cytochrome P450 expression, enhanced oxidative phosphorylation gene expression, and upregulation of FLVCR1 and ALOX5, reflecting coordinated rewiring of heme and lipid metabolism. Conclusions: In this pilot study, HCC and liver metastases demonstrated fundamentally different spatial architectures, with metastases uniquely harboring a germline/neural-like plasticity hub. Despite these organizational contrasts, both tumor types converged on a shared program of metabolic rewiring, highlighting potential therapeutic targets that link local tumor niches to systemic host–tumor interactions. Full article

Background: An artificial ovary has emerged as a novel alternative approach to prevent the reintroduction of cancerous cells after ovarian tissue autotransplantation. This study evaluates the ability of decellularized Wharton’s jelly (dWJ) to facilitate human ovarian follicle growth in a xenotransplantation model. Materials and Methods: Two transplanted groups were established; one consisted of a decellularized Wharton’s jelly/alginate (dWJ/Alg) composite, and an alginate (Alg) group was used as the control group. Each artificial ovary received approximately 20 partially isolated viable human ovarian follicles, subsequently undergoing xenotransplantation into ovariectomized, non-immunodeficient NMRI mice. Grafts were extracted at 1, 2, 4, or 5 weeks for comprehensive histological and immunohistochemical evaluations. Additionally, mouse blood serum was collected for hormonal analysis. Results: H&E staining confirmed granulosa cell proliferation and follicle growth in dWJ/Alg after 1 week of grafting. While human ovarian-like structures and cell proliferation were visible in other grafts, follicles were not observed. Conversely, immunohistochemical staining for Vimentin, Ki67, and CD45 confirmed the presence of human cells, proliferative cells, and inflammatory cells, respectively. However, hormonal assays revealed no significant difference in estrogen or progesterone levels between the experimental groups. Conclusions: It seems that Wharton’s jelly/alginate hydrogel can be used as an artificial niche for simulating the ovarian environment, effectively supporting the growth of xenotransplants of isolated human follicles. Full article

The growth plate is a specialized cartilage structure near the ends of long bones that orchestrates longitudinal bone growth during fetal and postnatal stages. Within this region reside a dynamic population of growth plate skeletal stem cells (gpSSCs), primarily located in the resting zone, which possess self-renewal and multilineage differentiation capacity. Recent advances in cell-lineage tracing, single-cell transcriptomics, and in vivo functional studies have revealed distinct subpopulations of gpSSCs, which are defined by markers such as parathyroid hormone-related protein (PTHrP), CD73, axis inhibition protein 2 (Axin2), forkhead box protein A2 (FoxA2), and apolipoprotein E (ApoE). These stem cells interact intricately with their niche, particularly after the formation of the secondary ossification center, through stage-specific regulatory mechanisms involving several key signaling pathways. This review summarizes the current understanding of gpSSC identity, behavior, and regulation, focusing on how these cells sustain growth plate function through adapting to biomechanical and molecular cues. Full article

Background/Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is a rare peripheral T-cell lymphoma of follicular helper T-cell (TFH) origin, often associated with immune dysregulation and EBV-positive B-cell proliferation. Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus 8 (HHV-8), typically arising in immunocompromised individuals. The synchronous occurrence of AITL and KS in HIV-negative patients is exceptionally rare, with only three cases previously reported worldwide. Case Presentation: We describe an 81-year-old HIV-negative Korean woman presenting with progressive generalized edema and dyspnea. Imaging revealed multifocal lymphadenopathy. Excisional biopsy of the inguinal lymph node showed two distinct but adjacent neoplastic processes. The AITL component demonstrated a polymorphous infiltrate of atypical TFH cells expressing CD3, CD4, CD10, PD-1, and Bcl-6, with monoclonal TCR-γ rearrangement and TET2 and RHOA mutations. The KS component comprised spindle cells with slit-like vascular spaces, red blood cell extravasation, and immunoreactivity for HHV-8, CD31, CD34, and ERG. The findings were consistent with a collision tumor. Despite supportive care, the patient’s condition deteriorated, and she was discharged with palliative care. Discussion: The coexistence of AITL and KS in an HIV-negative setting raises important pathogenetic considerations. AITL is characterized by profound immune dysregulation, with depletion of normal T-cell subsets, abnormal B-cell activation, and cytokine milieu changes that may favor latent viral reactivation. This immunologic environment may permit HHV-8 reactivation, thereby facilitating the development of KS even in the absence of overt immunodeficiency due to HIV infection. Our findings support the hypothesis that AITL-related immune dysfunction may create a permissive niche for HHV-8-driven neoplasia. Conclusions: This is the first reported case in Asia and the fourth worldwide of a collision tumor comprising AITL and KS in an HIV-negative patI dient. The case suggests that AITL-associated immune dysregulation may facilitate HHV-8 reactivation and KS development even in the absence of HIV infection. Awareness of this association is critical for accurate diagnosis and optimal patient management. Full article

Shiga toxins (Stx), produced by Shiga toxin-producing Escherichia coli, preferentially attack renal tissue and frequently induce acute kidney injury (AKI) and renal failure. To prevent irreversible damage, the injured renal tissue, particularly renal tubular epithelium, mounts a remodeling and regeneration response to repair itself. However, how such intrinsic renal repair processes are initiated and coordinated in infected renal tubular regions remains elusive. Herein, we reported that macula densa apparatus, in addition to its conventional role as a salt sensor in nephron, can function as an endogenous sensor for exogenous toxins (e.g., Stx). We demonstrated that macula densa cells orchestrate a rapid repair niche by initiating transcriptional activation of repair and regeneration factors in both Stx-injured murine models and human kidney organoids. Mechanistically, we showed that in response to Stx exposure, macula densa cells release a specific repair factor CCN1, which effectively promotes the regeneration of toxin-injured renal tubular epithelium and facilitates renal tubular repair through integrin-mediated signaling pathways. Moreover, we demonstrated that treatment with recombinant CCN1 can greatly ameliorate the structural damage and significantly restore the proximal tubular reabsorption capacity in Stx-infected kidney organoids. Our finding highlights a novel role of macula densa apparatus in toxin-induced renal injury, and paves a new avenue for treatment of AKI-associated renal diseases. Full article