Hematopoietic stem and progenitor cells in the bone marrow ensure continuous blood cell production. Homeostasis is controlled by a specialized microenvironment termed the niche. Extracellular vesicles released by the hematopoietic niche, both under normal and stress conditions, regulate stem cell maintenance, proliferation and differentiation. Here, we show that the Drosophila hematopoietic niche in the larval immune organ, the lymph gland, releases extracellular vesicles that mediate cell communication necessary to adapt blood cell progenitor homeostasis to immune stress. In response to wasp parasitism, ROS elevation in the niche causes the release of a heterogeneous population of EVs, including exosomes, which propagate and activate non-cell autonomously the EGFR pathway in lymph gland progenitors. Niche-derived exosomes promote progenitor differentiation into lamellocytes, a blood cell type dedicated to the neutralization of the pathogen. We further show that up-regulation of the metalloproteinase Mmp1 that occurs in niche cells in response to wasp infestation is required for exosome spreading through the niche's extracellular matrix. Our work establishes the Drosophila lymph gland as a novel in vivo model to study exosome-mediated cell communication and provides new insights into how niche-derived exosomes control immune stress hematopoiesis.
Aging tissues lose function in part because stem cells change in number and behavior, but how age-related changes in the stem cell niche drive these processes is not well understood. Using the fruit fly testis, we asked how aging of the niche microenvironment influences stem cell maintenance and competition. We show that levels of niche cell-derived bone morphogenetic protein (BMP) signals decline with age, leading to increased expression of the transcriptional corepressor Hairless in germline stem cells (GSCs). Elevated Hairless reduces the RNA binding protein Imp, causing loss of the stem cell factor Chinmo and triggering abnormal extracellular matrix accumulation, stem cell displacement, and niche deterioration. Overexpressing BMP signals in the niche, up-regulating Imp in GSCs, or depleting Hairless in GSCs ameliorate multiple aging-related defects. In contrast, GSC clones with low Imp or high Hairless outcompete their neighbors and take over the niche. These findings reveal how aging niche signals affect tissue decline and stem cell residence.
The resilience and robustness of the stem cell niche are critical for long-term tissue homeostasis, yet the molecular circuits that ensure this stability remain poorly understood. In the Drosophila ovarian germline stem cell niche, we investigate this fundamental question through the lens of adhesion, focusing on the role of N-cadherin in the somatic inner germarial sheath (IGS) cells. While the specific loss of N-cadherin alone is inconsequential, we discover that it becomes essential upon the loss of E-cadherin, revealing a critical, context-dependent function. This functional interplay is governed by a precise molecular circuit wherein E-cadherin cell-autonomously represses N-cadherin expression via a linear Wnt-mir-994 signalling axis. Strikingly, this regulatory relationship constitutes a cadherin switch, which is repurposed within the niche not to promote dispersal, but to enforce resilience. The E-cadherin-to-N-cadherin switch acts as a vital compensatory mechanism: the ectopic upregulation of N-cadherin upon E-cadherin depletion is essential to maintain IGS cell survival and their long cellular processes, thereby rescuing niche integrity and preventing GSC loss. Our study defines the function for N-cadherin in IGS cells, unveils the E-cadherin-Wnt-mir-994-N-cadherin axis and demonstrates the repurposing of a classic developmental module as a robustness circuit to safeguard the stem cell niche. This repurposed cadherin switch reveals an axis for targeting the resilience of niche-stem cell interplay, and also informs new strategies for stabilizing niche environments in regenerative medicine or targeting the resilient cancer stem cell microenvironment.
Acute myeloid leukemia (AML) remains a therapeutic challenge due to drug resistance and relapse, which are often driven by the protective bone marrow (BM) niche. Conventional xenograft models fail to adequately recapitulate this niche-specific pathophysiology. To overcome this limitation, a novel magnetically targeted intramedullary (MagIC-TI) xenograft model was developed. Magnetically labeled doxorubicin (DOX)-resistant HL60 cells (Mag-Re) were injected into the femurs of NSG (nonobese diabetic [NOD] Cg-PrkdcscidIL2rgtm1Wjl/SzJ) mice using a patented microinjection syringe under localized magnetic guidance. With the MagIC-TI model, rapid (day 1) and specific (100% by day 7) leukemic engraftment was achieved within the femoral BM, whereas intravenous (IV) injection led to delayed (mean 23.67 ± 10.26 days) and disseminated engraftment. Bioluminescence imaging, histopathological analysis, flow cytometry, and molecular assays confirmed that disease was localized in the MagIC-TI model. In contrast, extramedullary infiltration, predominantly in the lungs, spleen, liver, and kidneys, was observed early in progression in the IV model. The MagIC-TI model discriminated drug responses, showing effective tumor burden reduction with homoharringtonine (HHT) and unequivocal DOX resistance, a distinction that was obscured in heterogeneous IV models. Furthermore, employing a semisolid decalcification (SSD) system preserved green fluorescent protein (GFP) fluorescence, enabling high-resolution visualization of engrafted cells within bone tissue. The MagIC-TI model enables BM-targeted, rapid, and efficient leukemic engraftment and allows discrimination of drug sensitivity and resistance. This model provides a robust and reproducible platform for modeling the leukemia BM niche and for preclinical evaluation of niche-directed therapies.
Madhuca hainanensis is an endangered plant species endemic in Hainan, China. We conducted vegetation surveys for both the tree and shrub layers of M. hainanensis communities in Diaoluoshan and Jianfengling to explore species composition, floristic distribution patterns, diversity, community stability, and niche characteristics, which could provide a scientific basis for species conservation and population recovery in these areas. The results showed that Lauraceae was the dominant family among associated tree species in both sites, and the overall species composition exhibited distinct tropical floristic traits. There were no significant differences in α-diversity indices (Margalef index, Simpson index, Shannon index and Pielou index) of tree layer between the two sites, indicating broadly convergent community structural feature. In contrast, shrub layer at Jianfengling showed significantly higher Margalef (7.03) and Shannon (3.08) indices than at Diaoluoshan (4.61 and 2.59, respectively), reflecting greater species richness. Both sites exhibited significant β-diversity in both tree and shrub layers, indicating pronounced spatial differentiation in species composition. Cyclobalanopsis patentilimba and Castanopsis carlesii displayed relatively broad niche breadths (5.79 and 5.51, respectively) and high importance values (4.1% and 3.9%, respectively), jointly as constructive species alongside M. hainanensis and playing critical roles in maintaining community structure and ecological function. Species composition and structure of M. hainanensis communities in the two sites exhibited significant spatial difference, providing irreplaceable ecological value for regional biodiversity conservation and the preservation of germplasm resources of plant species with extremely small populations. On the basis of strengthening in-situ conservation, moderate artificial intervention should be implemented on tree species with high niche overlap with M. hainanensis, such as Schima superba (0.83) and Castanopsis fissa (0.91). When carrying out ex-situ conservation, species with niche complementarity with M. hainanensis, such as Acronychia pedunculata and Diospyros howii, could be preferentially selected to reduce the pressure of interspecific competition. 海南紫荆木为海南特有濒危植物。本研究以吊罗山和尖峰岭林区的海南紫荆木群落为研究对象,对其乔木层和灌木层开展植被调查,分析群落物种组成、区系分布、多样性、稳定性及生态位特征,为物种保护与种群恢复提供科学依据。结果表明:吊罗山与尖峰岭林区海南紫荆木的伴生树种均以樟科为第一优势科,两地物种组成表现出明显的热带区系特征。2个林区乔木层α多样性指数(Margalef指数、Simpson指数、Shannon指数、Pielou指数)差异均不显著,群落物种结构特征整体趋同;尖峰岭林区灌木层Margalef指数(7.03)和Shannon指数(3.08)显著高于吊罗山(4.61和2.59),物种丰富度更高。两地乔木层和灌木层的β多样性均达到显著水平,表明群落物种组成具有明显的空间分异。托盘青冈与米槠均具有较高的生态位宽度(5.79和5.51)和重要值(4.1%和3.9%),与海南紫荆木共同构成群落的主要建群种,在群落结构与功能维持中起重要作用。2个林区海南紫荆木群落物种组成与结构存在明显空间差异,在区域生物多样性保护和极小种群种质资源保存中具有不可替代的生态价值。建议在加强就地保护的基础上,对与海南紫荆木生态位重叠度较高的木荷(0.83)、黧蒴锥(0.91)等树种进行适度人工干预;在开展异地保护时,可优先选择山油柑、琼南柿等与海南紫荆木生态位互补的物种作为伴生树种,以降低种间竞争压力。.
Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synthesizes emerging evidence positioning MPN-associated thrombosis as a distinct pathobiologic entity, clonal thrombo-inflammation, driven by the convergence of somatic mutations and innate immune activation. We examine the continuum from clonal hematopoiesis of indeterminate potential (CHIP) to overt MPN, highlighting how Janus kinase 2 (JAK2)V617F and other driver mutations reprogram myeloid cells toward hyperinflammatory phenotypes. A recurring mechanistic theme is NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 family signaling, which may create a feed-forward loop in which mutant clones amplify inflammatory circuits that, in turn, may enhance clonal fitness and contribute to thrombogenicity across multiple cellular compartments. We propose the 'thrombotic niche' as a conceptual, multi-compartment model encompassing mutant hematopoietic stem cells, hyperinflammatory myeloid effectors, hyperreactive platelets, platelet-leukocyte aggregates, and activated endothelium, but it remains a hypothesis-generating framework that lacks direct prospective clinical validation. Current cytoreductive strategies inadequately address this underlying biology, leaving substantial residual vascular risk. Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.
Stress tolerance underpins ecological plasticity and niche expansion in fungi. Although Trichoderma is best known from sylvan, mycoparasitic, soil-, and plant-associated habitats, its occasional recovery from saline soils raises questions about the molecular basis of this adaptation. A coastal survey revealed limited but persistent Trichoderma diversity with frequent recovery of halotolerant T. asperelloides. Screening a salt-stressed T. asperelloides cDNA library in Saccharomyces cerevisiae identified 62 inserts, of which 12 were salt responsive in vivo. Deletion of gld1, encoding an aldo-keto reductase, impaired halotolerance and glycerol accumulation. In a 27-species synthetic community, the Δgld1 mutant was competitively displaced by other species under salinity. Cross-species promoter replacement in a salinity-sensitive strain T. atroviride increased its halotolerance. A global tef1 haplotype network placed the coastal isolates within broader T. asperelloides diversity, consistent with recurrent expansion into saline/coastal soils. Together, these findings link accessory-gene regulation to niche expansion in fungi.
Ectomycorrhizal fungi (EMF) play critical roles in nutrient exchange, soil processes, and plant community structure, yet the mechanisms linking their environmental interactions to reproduction remain poorly understood. The black truffle (Tuber melanosporum) provides a model for studying these dynamics through its formation of brûlés-vegetation-free zones around a host plant and associated with fructification. Although prior studies have associated truffle production with factors such as pH, carbonates, and specific microbial groups, most work has been limited by narrow parameter ranges, uncontrolled confounders, and an absence of direct fruiting measurements, leaving unresolved whether these patterns facilitate reproduction or merely accompany it. Here we address these limitations using a broad paired design sampling 93 trees with and without brûlés across productive and unproductive North American orchards. We show that fruiting consistently aligns with distinct soil chemical profiles -including reduced organic matter and nitrogen, and elevated iron and magnesium-and with highly structured microbial communities. Fruiting soils exhibited the highest bacterial and fungal diversity, strong beta-divergence from non-fruiting soils, and enrichment of chemoheterotrophic guilds capable of mobilising nutrients and accelerating organic matter turnover. Network analyses revealed that productive soils support more cohesive and functionally integrated microbial consortia, despite only modest shifts in taxonomic composition. These patterns suggest that T. melanosporum reproduction depends not solely on favourable edaphic conditions, but on active niche construction at the soil chemical-microbial interface. Our findings highlight a previously underappreciated reproductive dimension of EMF ecosystem engineering, with implications for truffle cultivation, sustainable land management, and broader mycorrhizal ecology.
Only subset of patients with Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy and this is partly due to limited understanding of how oncogenic mutations shape the tumor microenvironment (TME). To define how EGFR and KRAS mutations influence the spatial organization and immune composition of the NSCLC TME. We conducted 38-marker high-plex immunofluorescence to 197 NSCLC tumors (>2 million cells) stratified by EGFR and KRAS genotypes. Quantitative phenotyping and spatial analyses, including cellular neighborhoods (CN), nearest neighbors (NNs = 5-20), and spatial proximity profiling (25-100 μm), were performed to assess immune architecture and clinical correlations. EGFR- and KRAS-mutant tumors showed higher tumor cell density and reduced immune infiltration compared with wild-type tumors. Both mutation types were associated with depletion of cytotoxic T cells, dendritic cells, and granulocytes, while EGFR-mutant tumors showed enrichment of M2-like tumor-associated macrophages (TAMs). CN-analysis identified 14 spatial clusters, with reduced cytotoxic and helper T cell-rich neighborhoods in mutant tumors. NN-analysis revealed shorter distances between M2-like TAMs in EGFR-mutant tumors and greater immune exclusion in non-mutants. Spatial proximity revealed higher densities of T-regs, TAMs near tumor cells in KRAS-mutant tumors. All spatial metrics correlated significantly with prognosis in Cox proportional hazards models, highlighting immune cell positioning as an important predictor of outcome. EGFR- and KRAS-mutant tumors remodel the NSCLC immune landscape, creating distinct immunosuppressive and immune-excluded niches. Spatial proteomics reveals prognostic immune architectures that may guide mutation-directed immunotherapy strategies.
Adult-onset dermatomyositis (DM) is an autoimmune inflammatory myopathy with distinct cutaneous manifestations and a strong association with malignancy. Through comparative analysis with cutaneous lupus erythematosus (CLE), our integrated spatial and single-cell transcriptomics analysis reveals unique immune and stromal niches associated with DM subtypes. We find that cancer-associated DM skin lesions are distinguished by the presence of dispersed immune infiltrates enriched with macrophages or organized lymphoid aggregates with dense B cell cores surrounded by CD4 + /CD8 + T cells, accompanied by preserved vascular architecture. In contrast, non-cancer-associated DM skin is characterized by dense myeloid cell infiltrates, harbouring elevated expression of IL1B and CXCL10 localizing near injured vascular endothelia. Cytokines produced by these myeloid infiltrates, together with local tissue hypoxia, trigger dramatic stromal remodelling, leading to loss of vascular-associated fibroblasts. In addition to the CXCL10+ myeloid signature, non-cancer-associated DM skin is characterized by specific cellular pairs: PD-L1-expressing mature dendritic cells enriched in immunoregulatory molecules (mregDC) and activated regulatory T cells (Treg) expressing NFKB2 and TNF receptors. While both DM and CLE show strong interferon signatures, DM uniquely displays IFNβ expression. Together, our study provides a comprehensive spatial mapping of immune and stromal cells in adult-onset DM.
Background: Prostate cancer (PCa) responds poorly to immunotherapy. We investigated the myeloid checkpoint TIM3 (HAVCR2) to define its lineage localization and regulatory logic in the PCa microenvironment. Methods: We integrated stage-resolved public single-cell RNA-seq datasets spanning primary PCa, metastatic hormone-sensitive PCa, and castration-resistant PCa. Myeloid compartments were analyzed via differential expression, regulon inference, and ligand-receptor modeling. Clinical relevance was evaluated in the Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) cohort and independent cohorts using a myeloid TIM3 signature. Mechanistic validation was achieved through PR domain zinc finger protein 1 (PRDM1) chromatin immunoprecipitation followed by Chromatin Immunoprecipitation (ChIP)-qPCR (ChIP-qPCR), TIM3-promoter luciferase assays, and functional perturbation of the galectin 9 (LGALS9)-TIM3 signaling pathway in macrophages differentiated. Results: TIM3 expression was predominantly confined to monocytes/macrophages, indicating TIM3 as a microenvironmental checkpoint in PCa. TIM3_high macrophages formed a Secreted Phosphoprotein 1 (SPP1)-enriched tumor-associated macrophage (TAM) state coupled to chemokine programs and extracellular matrix remodeling. Regulon profiling nominated PR domain zinc finger protein 1 (PRDM1) as an upstream driver; PRDM1 correlated with TIM3. Communication inference further highlighted an LGALS9-TIM3 axis and a C-X-C motif chemokine receptor 4/integrin subunit beta 1 (CXCR4/ITGB1)-associated permissive niche. Recombinant LGALS9 induced TIM3-linked M2-like macrophages polarization and increased CXCR4/ITGB1, which was attenuated by TIM3 blockade. Conclusions: Our results delineate a PRDM1-licensed TIM3_high macrophage program sustained by an LGALS9-TIM3 reinforcement loop and coupled to immunosuppressive and remodeling-associated phenotypes. Targeting TIM3 in the myeloid compartment, alone or in rational combinations, may represent a feasible strategy to reprogram tumor-associated macrophage states in PCa.
Ex vivo expansion of human adipose-derived stem cells (hADSCs) remains challenging because reduced-serum culture conditions can compromise short-term cell function. Here, we evaluated a microenvironment-inspired tri-component preconditioning regimen composed of platelet-rich plasma (PRP), Lactobacillus plantarum cell-free supernatant (Lp-SN), and resveratrol-loaded PLGA nanoparticles (RSV-PLGA-NPs) as a reduced-serum culture support strategy. Using a Box-Behnken design, we identified a formulation space in which PRP, Lp-SN, and RSV-PLGA-NPs were associated with improved hADSC viability and increased expression of selected stemness-associated genes in vitro. Omission-control experiments comparing the full formulation with partial combinations and blank PLGA NPs showed attenuated responses when individual components were removed, whereas the NP carrier alone had no significant effect. These findings support the utility of this tri-component system as a preliminary ex vivo preconditioning approach for short-term hADSC culture support. However, the results should be interpreted within the limits of the present in vitro study, as long-term expansion, post-treatment differentiation capacity, and in vivo performance were not evaluated.
Regeneration is an essential pathway for the continuity of tree populations and a critical ecological process for the maintenance and restoration of natural forest ecosystems. Seed regeneration and sprout regeneration represent two strategies shaped by long-term evolution, reflecting adaptive trade-offs in response to resource limitations and environmental disturbances. In the context of global change, such trade-off is undergoing profound alteration. Based on regeneration niche theory, we reviewed the biological foundations and ecological significance of seed regeneration (colonization niche) and sprout regeneration (persistence niche) in tree species, with a focus on the mechanisms of global climate change, shifting in disturbance regimes, and habitat fragmentation that influence these two regeneration strategies. There are deficiencies in current research regarding the systematic analysis of the formation and evolution mechanisms of different tree species' preference for regeneration, the physiological and molecular mechanisms of shoot occurrence, the methodological challenges in multi-dimensional quantification of regeneration niches and their responses to global change, the need for further research on the response of forest tree regeneration strategies under global change, and the insufficient integration of the regeneration niche theory and forest management practices. Future efforts should be made to strengthen the molecular ecological and systems biological basis for the evolution of forest tree regeneration trade-off strategies under global change, to quantify the conversion thresholds of tree seedling regeneration and shoot regeneration, to construct a multi-dimensional research framework for forest tree regeneration niches, to strengthen the research on the response mechanisms of main forest tree species' regeneration strategies under global change, and to promote the deep integration of forest tree regeneration trade-off theory and forest management practices. These efforts would provide scientific basis for the sustainable management and ecological restoration of forests. 森林天然更新是森林生态系统维持与恢复的关键生态过程,也是林木种群延续的重要途径。种子更新与萌蘖更新作为林木在长期进化中形成的两种策略,体现了其对资源限制与干扰环境的适应性权衡。在全球变化背景下,这一权衡关系正发生深刻变化。本文基于更新生态位理论,梳理了林木种子更新(定居生态位)与萌蘖更新(驻留生态位)的生物学基础与生态学意义,探讨了全球气候变化、干扰格局改变及生境破碎化对两类更新策略的影响机制。现有研究主要存在的问题:缺乏对不同造林树种更新偏好的形成与进化机制成因的系统解析,萌蘖发生的生理与分子机制研究薄弱,更新生态位的多维度量化及其对全球变化的动态响应面临方法学挑战,林木更新策略对全球变化的响应研究有待深化,更新生态位理论与森林经营实践的结合尚显不足。今后应加强解析全球变化背景下林木更新权衡策略进化的分子生态学与系统生物学基础、量化林木种子更新与萌蘖更新的转化阈值、构建林木更新生态位的多维研究框架、强化全球变化背景下主要造林树种更新策略的响应机制研究,推动林木更新权衡理论与森林经营实践的深度融合,为森林可持续经营与生态恢复提供科学依据。.
Bone defects remain a significant challenge in orthopedics, and despite the widespread use of mesenchymal stem cells (MSCs) in regenerative medicine, their therapeutic performance in vivo often falls short of expectations. Emerging evidence suggests that the local microenvironment particularly age-related or injury-induced cellular senescence may compromise MSC function. In this study, we investigated how a senescent vascular niche arising after bone injury influences MSC proliferation, differentiation, and its possible mechanisms involved in regeneration and clearing of the aging microenvironment. A femoral trochlear defect was created in 3-month-old SD rats (n = 6/group) to characterize temporal senescence changes using SA-β-Gal staining, p16/CD31 immunofluorescence, and expression of Cdkn1a/Cdkn2a. Primary endothelial cells (ECs) were isolated and senescence-induced with 400 µM H₂O₂ for 45 min. MSCs were co-cultured with senescent ECs (SnECs) in 3D collagen I hydrogels (2 mg/mL, ~ 5 kPa). Quercetin, selected from DrugAge screening (20 µM), was incorporated into a 4 wt% thermosensitive hydrogel (TSH-Q) to enable 7-day sustained release. Bone regeneration was assessed by µCT, histology, and immunofluorescence at 1 and 4 weeks post-injury. Bone defects triggered a biphasic senescence response: early senescence occurred predominantly in peri-defect osteocytes at 1 week, while robust senescence was later observed in neovascular endothelial cells by week 4. SnECs significantly impaired MSC biological functions, reducing migration, chondrogenic differentiation (Safranin O intensity), and mineralization (Alizarin Red) (all p < 0.01). Local delivery of quercetin via TSH-Q cleared approximately 81% of p16⁺ endothelial cells in vivo and enhanced bone repair, increasing BV/TV compared with unloaded TSH (p < 0.001). In the early stage of bone defects, aging cells mainly represent bone cells in the tissues surrounding the bone defect. At later staged, with no changes in the microenvironment, the aging of vascular endothelial cells in the new tissues and blood vessels was most significant. We successfully induced endothelial cell senescence and further explored the functional impact of SnECs on MSCs and found that aging ECs led to a decline in MSCs effects in aging, including reduced proliferation, chondrogenic differentiation, osteogenic differentiation, tissue repair, and mineralization. The therapeutic effects of MSCs and the repair of bone defects were effectively promoted by constructing a quercetin thermosensitive hydrogel sustained-release system to improve the aging microenvironment of bone defects. Bone injury generates a senescent vascular niche that markedly disrupts MSC-mediated regeneration. Targeted rejuvenation of this niche using sustained-release quercetin effectively restores MSC function and significantly accelerates bone reconstruction. These findings highlight the aging microenvironment as a key therapeutic target for improving MSC-based treatments for bone defects.
Oral squamous cell carcinoma (OSCC) is characterized by high aggressiveness. This study aims to elucidate the role of NDRG1 in the evolutionary heterogeneity and spatial microenvironmental remodelling of OSCC. By integrating bulk transcriptomics, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST), complemented by in vivo and in vitro functional assays, we systematically explored the regulatory logic of the MSTRG.47889/miR-1299/NDRG1 axis. The MSTRG.47889/miR-1299/NDRG1 ceRNA regulatory axis was identified and validated, demonstrating its significant role in promoting OSCC proliferation and invasion while impairing cellular adhesion. Single-cell analysis revealed a significant expansion of the NDRG1-high subpopulation in tumour tissues, which drives cellular evolution along a pseudotime trajectory toward a partial epithelial-mesenchymal transition (p-EMT) and a high glycolytic state. Spatial transcriptomics analysis revealed that NDRG1 is highly expressed within 'hypoxia-metabolic' niches. Our integrative analysis suggests that these regions may coordinate with endothelial cells, highlighting a potential role for the ANGPTL4-CDH5 signalling axis in promoting a proangiogenic microenvironment. These findings provide preliminary insights into how NDRG1 serves as a pivotal regulator driving p-EMT and coordinating niche remodelling. NDRG1 serves as a pivotal regulator driving p-EMT and proangiogenic niche remodelling, representing a potential novel target for the diagnosis and treatment of OSCC.
Plant-associated microbiomes are key contributors to plant nutrition and stress tolerance, particularly in arid ecosystems where extreme abiotic conditions strongly shape plant-microbe interactions. Despite this, the abiotic drivers of microbiome assembly across different plant compartments in wild medicinal species from these environments remain poorly understood. In this study, we investigated bacterial community structure across multiple niches, including bulk soil, rhizosphere, root, and shoot, in three wild Artemisia species (Artemisia herba-alba Asso., Artemisia negrei L., and Artemisia mesatlantica Maire), the latter two being endemic to arid regions of Morocco. Using amplicon sequencing, we observed diverse bacterial associations with each plant niche harboring distinct taxa. Host plant species significantly influenced bacteriome composition (p = 0.026), particularly in Artemisia mesatlantica, which hosted the most specific bacterial taxa compared to its other relatives. Plant compartment emerged as key drivers of belowground bacterial community assembly with additional structuring by host species and edaphic factors. Soil pH, calcium carbonate content, organic matter and electrical conductivity were strongly correlated with shifts in bacterial diversity and composition, emphasizing the role of soil physicochemical properties as an environmental filter under extreme alkaline and arid conditions. Despite these species- and environment-specific variations, a conserved core bacteriome was identified across all Artemisia species, and compartments except shoot, comprising of Bacillus, Microvirga and Rhizobium. Our results demonstrate that the interplay between host identity and soil properties orchestrates distinct, yet functionally coherent bacterial communities in wild Artemisia species. Bacterial taxa identified as core are well-known for their roles in plant growth promotion, biocontrol and production of bioactive secondary metabolites. The persistence of this core bacterium comprising of Bacillus, Microvirga and Rhizobium suggests a stable association across hosts and compartments, potentially reflecting conserved ecological roles, although functional contributions were not directly assessed in this study. Overall, our findings reveal how the interplay between soil properties and host identity shapes the assembly of distinct, yet compositionally consistent bacterial communities in wild medicinal Artemisia species.
Perineural invasion (PNI) is an aggressive driver of tumor progression, therapeutic resistance, and poor prognosis across diverse malignancies. Traditionally viewed as a tumor cell-autonomous process, PNI is increasingly recognized as a dynamic phenomenon shaped by the tumor-nerve-stromal ecosystem. This review synthesizes recent advances to reframe neural invasion as a coordinated, multicellular process governed by reciprocal interactions within this niche. We delineate how stromal and immune components, including cancer-associated fibroblasts, Schwann cells, immune cells, and the extracellular matrix, facilitate PNI through structural remodeling and biochemical signaling within the tumor-nerve interface. These coordinated interactions drive nerve reorganization and local immune reprogramming, collectively establishing a permissive niche that supports tumor spread along neural routes. By integrating these interconnected mechanisms into a neuro-ecological framework, we clarify how networked tumor-stromal-neural remodeling underlies neural dissemination. This perspective identifies therapeutic vulnerabilities within the neural microenvironment and suggests that disrupting bidirectional crosstalk between tumor cells and their stromal partners may offer strategies to limit neural spread and improve clinical outcomes.
Understanding the ecological links in the microbiome of Camellia sinensis is vital for exploring beneficial interactions between microorganisms and economically important woody plants. This study investigates the characteristics of microbial communities, source-sink dynamics, driving factors, and functional differentiation of tea tree bark and bulk soil in the primary tea-producing regions of Yunnan, China (City of Pu'er, Lincang, and Xishuangbanna). Using amplicon sequencing, FEAST source tracking, and functional prediction, we analyzed microbial community differences and ecological roles. Findings revealed that bulk soil may served as the microbial reservoir for bark, sharing all bark bacteria and 68.09% of bark fungi in Pu'er, with minimal reverse flow. Soil harbored higher alpha diversity dominated by Chloroflexi, Acidobacteriota, and Sordariomycetes, while bark selectively enriched Gammaproteobacteria, Cyanobacteriia, and Lecanoromycetes. Plant type mainly influenced bark bacterial communities (R²=76.49%, P < 0.001), whereas geographic location significantly impacted soil bacterial composition (R²=45.72%, P < 0.001) and fungi in both bark (R²=63.06%, P < 0.001) and soil (R²=78.84%, P < 0.01). Total nitrogen (TN) and organic matter (OM) in bulk soil emerged as the predominant factors influencing community variation both for niches of soil and bark. Functional differentiation was observed, with soil microbiomes primarily engaged in chemoheterotrophy and nutrient cycling, while bark microbiomes were more involved in carbon fixation and stress resistance. LEfSe analysis identified 30 bacterial and 64 fungal biomarkers (LDA ≥ 4, P < 0.05), including Xanthobacteraceae in soil and Pleosporaceae in bark. This study highlights soil's crucial role as a microbial reservoir and the impact of niche-specific factors, providing a framework to understand how microbial diversity is maintained and regulated along the Soil-Bark Continuum in tea plants.
Glioblastoma (GBM) represents the most aggressive primary brain tumor in adults, characterized by a profoundly immunosuppressive tumor microenvironment (TME) that systematically disables cytotoxic lymphocyte function and renders conventional immunotherapy largely ineffective. While exhaustion of CD8+ T cells and natural killer (NK) cells within solid tumors has been extensively studied in other cancer types, the CNS-specific architectural, metabolic, and molecular constraints that shape cytotoxic lymphocyte heterogeneity in GBM remain insufficiently characterized. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial multiomics have begun to reveal a rich landscape of cytotoxic lymphocyte subpopulations in GBM. These include TCF-1+ progenitor-exhausted T cells (Tpex), terminally exhausted CD8+ T cells (Tex), and dysfunctional natural killer (NK) cell subsets, each distributed across anatomically distinct immune niches. This review synthesizes current knowledge across three interconnected areas: the single-cell atlas of GBM-infiltrating cytotoxic lymphocytes; the spatial organization of their dysfunction within perinecrotic, perivascular, and infiltrative-edge niches; and the epigenetic and transcriptional programs that underlie GBM-specific cytotoxic failure, including dysregulation of the TOX/TCF-1 axis and IDH-mutation-driven silencing of NKG2D ligands. Critically, we compare CD8+ T cell and NK cell exhaustion mechanisms, highlighting their mechanistic divergence and therapeutic implications. We further discuss how these multiomics insights can be translated into neurosurgically relevant strategies, including intraoperative tumor profiling, progenitor T cell expansion via epigenetic priming, NKG2A/TIGIT dual blockade, and intracavitary delivery of engineered NK cells. Together, this review proposes a spatially and cellularly resolved framework for understanding cytotoxic immune failure in GBM and outlines precision immunotherapy approaches tailored to the unique immunobiology of the CNS tumor microenvironment.
Interstitial macrophages (IMs) are increasingly recognized for their vital roles in maintaining tissue homeostasis and orchestrating immune responses. Building on earlier work showing that two overarching IM subsets, CD206hi and CD206lo, encompass ten unique chemokine-expressing subpopulations that regulate immune cell recruitment and tertiary lymphoid structures, we sought to further define the molecular programs, potential divisions of labor, and spatial organization of murine lung IMs. We performed a comprehensive transcriptomic analysis of murine lung IMs and integrated these data with Xenium spatial transcriptomics to examine IM subset-associated gene programs and localization within the lung microenvironment. Differential gene expression across IM subsets is summarized in accompanying tables. CD206hi and CD206lo IM subsets exhibited distinct cytokine and receptor gene profiles, along with a predicted autocrine network that may influence their migration and cytokine-driven functions. IM subsets also displayed distinct innate immune signatures, including complement components, scavenger receptors, and pattern recognition receptors, such as Toll-like receptors and C-type lectins. Using Xenium spatial transcriptomics, we found that IMs in our dataset predominantly localized to three lung regions: bronchovascular bundles, interstitium, and periphery. CD206hi and CD206lo IMs preferentially occupied specific anatomical niches, associated with differential integrin and metallopeptidase gene expression. Chemokine expression within IMs also showed distinct spatial localization patterns associated with the positioning of T cells and B cells. Overall, our findings advance the understanding of IM heterogeneity and identify molecular programs associated with chemoattraction, inflammation regulation, innate immune defense, and tissue maintenance, while providing a high-resolution framework for investigating their localization, interactions, and contributions to lung immunity and disease.