Biology subjects

Yang, X.

Publications and source records attributed to Yang, X..

At least 109 records · Page 6Linked to original sources

bioRxiv2026

Neuronal UBE3A loss engages a TNF-driven neuron-to-microglia axis that promotes synapse remodeling

Neuron-microglia communication shapes neuroimmune homeostasis and circuit maturation, yet the neuron-derived cues that tune microglial inflammatory state and phagocytic programs remain incompletely defined. The E3 ubiquitin ligase UBE3A is critical for brain development and synaptic function, and altered UBE3A dosage or activity is linked to neurodevelopmental phenotypes with emerging connections to inflammation. Using Angelman syndrome (AS), where UBE3A loss is largely neuron-selective due to imprinting, as a tractable framework, we investigated how neuronal UBE3A deficiency engages microglial programs. In human iPSC-derived neuron-microglia co-cultures, neuronal UBE3A depletion induced a TNF-associated secretory signature and was accompanied by increased microglial inflammatory markers, including complement components. Neuron-conditioned media was sufficient to elicit microglial cytokine/complement transcripts, supporting a role for soluble neuron-derived cues. In these co-cultures, neuronal UBE3A loss increased synapse engulfment by microglia, which was reduced by TNF receptor pathway inhibition with the TNFR1 antagonist R7050 alongside decreased microglial inflammatory readouts. In vivo, juvenile AS mouse hippocampus showed early microglial dysregulation, and reanalysis of a maternal-deletion AS pig single-nucleus RNA-seq dataset revealed enrichment of microglial activation and phagosome/lysosome pathways. Together, these findings implicate a TNF-linked neuron-to-microglia signaling axis downstream of neuronal UBE3A loss that can be pharmacologically modulated during development.

neuroscience↗

bioRxiv2026

SOX8-USP7-PGC-1α axis enhances thermogenesis in brown adipocytes

Obesity is one of the most prevalent diseases worldwide. Increasing thermogenesis to enhance energy expenditure has emerged as a promising therapeutic strategy. In an effort to identify new regulatory targets in thermogenic adipocytes, we found that SOX8 is correlated with obesity and serves as a novel marker of classical brown adipocytes in both humans and mice, upregulating during acute cold exposure. Functional studies further demonstrated that adipocyte-specific knockdown of SOX8 leads to obesity and metabolic dysfunction in mice. Mechanistically, SOX8 directly interacts with USP7 and stabilizes PGC-1 by reducing its K48-linked polyubiquitination. AAV-Rec2-mediated SOX8 overexpression initially enhanced energy expenditure, improved insulin sensitivity, and alleviated metabolic dysfunction in HFD-fed mice. However, prolonged SOX8 overexpression induced compensatory metabolic maladaptation, characterized by reduced energy expenditure, impaired glucose homeostasis, and mitochondrial structural disruption. These findings reveal a novel SOX8-USP7-PGC-1 regulatory axis in brown adipocytes, and reveal a previously unrecognized time-dependent effect of sustained thermogenic activation, highlighting SOX8 as a promising therapeutic target for obesity and metabolic syndrome.

cell biology↗

bioRxiv2026

Decoding Immune Reconstitution Failure in People Living with HIV through Single-cell Genomics

Immune non-responders (INRs), a subset of people living with HIV (PLWH), fail to achieve full immune reconstitution and remain at increased risk of morbidity, mortality, and non-AIDS-related illnesses. As the mechanisms underlying this impaired immune recovery remain poorly understood, we performed single-cell multi-omics profiling on peripheral blood mononuclear cells from 43 INRs, 47 immune responders and 53 healthy donors. Our dataset comprises 2,744,009 transcriptomes and 1,226,658 chromatin-accessibility profiles across 58 identified immune cell types. INRs exhibited markedly elevated inflammatory signaling, increased apoptotic activity, and dysregulation of immune-activating ligand-receptor interactions. Additionally, we identified 2,996 interaction cis-eGenes and 5,938 cis-caPeaks, and validated key cell type-specific cis-xQTL effects associated with immune reconstitution failure. Furthermore, we identified 3,551 sc-eQTLs and 872 cell-state interaction eQTLs (ieQTLs) in CD4+ T cells. A genotype-specific upregulation of OAS3 in INRs, likely regulated by STAT1, was identified based on these results. We developed scPRISM (single cell Predictive Reconstitution Immune Status Model), a multi-modal framework that integrates scRNA-seq and scATAC-seq data to perform the dual tasks of differentiating disease states and predicting gene expression from chromatin accessibility, thereby deciphering the cell type-specific cis-regulatory basis of the disease. Our study delineates the transcriptional and epigenomic landscape of immune dysregulation in INRs and provides new genetic insights into HIV-associated immune reconstitution failure. These findings offer a foundation for developing biomarkers and precision therapies to restore immune function in PLWH.

genetics↗

bioRxiv2026

Comprehensive Complete-Genome Analysis of Lactobacillaceae and Bifidobacteriaceae Reveals Strain-Specific Metabolic Interactions in Chinese Gut Microbiota

Bifidobacteriaceae and Lactobacillaceae are key probiotic families and widely used in food production, yet a comprehensive understanding of strain functions and their gut microbial interactions based on complete genomes remain understudied. Here we constructed a complete-genome dataset of 3,300 strains from these two families, including 1,151 newly isolated from China. Compared with draft assemblies, complete genomes substantially recovered a gene functional landscape encompassing stress tolerance, surface exopolysaccharide synthesis, nutrient utilization, and mobile genetic elements. Major species from both families exhibited a prevalence >60% in the Chinese population, far higher than that in US/Dutch cohorts. Notably, as a core probiotic species with remarkable genomic plasticity and gut-adaptive potential, Lactiplantibacillus plantarum stood out in our dataset for its enriched functional profile and was particularly abundant in the Chinese population. Moreover, compared with non-Chinese genomes, our isolates of key species displayed less metabolic complementarity and stronger competition with potentially pathogenic keystone species in the gut, thereby linking strain origin to enhanced probiotic potential and ecological fitness to benefit human gut health.

microbiology↗

bioRxiv2026

Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome

Mutations that reduce UBE3A cause Angelman syndrome (AS), a neurodevelopmental disorder marked by severe developmental delay and neuropsychiatric symptoms. Although UBE3A has been studied primarily in neurons, it is also expressed in the oligodendrocyte lineage, raising the possibility that glial dysfunction contributes to disease phenotypes. Here we identify an intrinsic, UBE3A-dependent mechanism that governs oligodendrocyte precursor cell (OPC) homeostasis, a process necessary for normal myelination. Using human iPSC-derived OPCs, we performed a targeted compound screen and found that loss of UBE3A diminishes estrogen receptor-{beta} (ESR{beta}) signaling, leading to impaired OPC self-renewal. Mechanistically, UBE3A sustains ESR{beta} levels in OPCs and thereby maintains downstream signaling required for OPC proliferation and stable OPC density. To address cell-type specificity and neuron-glia interactions, we combined oligodendrocyte-lineage-restricted Ube3a knockdown in vivo with reductionist iPSC neuron-OPC co-culture assays, which together support an intrinsic requirement for oligodendroglial UBE3A in OPC proliferation and myelination. Pharmacologic activation of ESR{beta} with selective agonists restored OPC self-renewal and myelination deficits in AS patient iPSC-based systems and rescued oligodendroglial and behavioral abnormalities in AS mouse models. Notably, ESR{beta} signaling primarily regulates OPC homeostasis rather than directly driving oligodendrocyte differentiation, pinpointing a stage-specific therapeutic entry point. These findings highlight a tractable oligodendroglial pathway downstream of UBE3A with translational potential for AS. One Sentence SummaryUBE3A regulates oligodendroglial homeostasis for myelination via estrogen receptor-{beta} signaling as a therapeutic target for Angelman syndrome.

neuroscience↗

bioRxiv2026

Benchmarking Static Gene Regulatory Network Reconstruction and Dynamic Transition Probing in Single-Cell Foundation Models.

Single-cell foundation models may encode gene regulatory information, but it remains unclear which model components capture this signal and how it compares with conventional inference methods. Here, we introduce a unified benchmark that evaluates gene regulatory network (GRN) reconstruction from six single-cell foundation models and three classical baselines across six datasets and four reference network types. We disentangle three sources of regulatory signal within each model--pretrained token embeddings, final-layer hidden states, and attention-derived scores. Under a strict zero-shot setting, scGPT token-embedding similarity outperforms classical baselines on STRING and ChIP-seq references, recovers core transcription factors, and best preserves reference network topology. Moreover, static GRNs cannot test whether learned gene-gene relationships are predictive of expression dynamics, we therefore introduce dynamic transition probing, which iteratively applies a models reconstruction head to drive early-cell profiles toward late-cell states without temporal supervision. We find pretrained models capture meaningful developmental transitions, with scFoundation showing the strongest overall performance. Together, our results show that single-cell foundation models encode transferable regulatory and dynamical priors, but how well these priors can be recovered depends on model architecture, pretraining design, and extraction strategy.

systems biology↗

bioRxiv2026

Non-enzymatic RNA Glycation is a Metabolic Sensor of Cellular Stress

Non-enzymatic RNA modifications expand the epitranscriptome, encoding a rapid and chemistry-driven response to cellular stress. While methylglyoxal, a reactive glycolytic byproduct of metabolic stress, has been shown to modify proteins and DNA, its impact on RNA has remained unexplored. Here, we identify mRNA as a dynamic substrate of MGO, whose modification is actively regulated by DJ-1 and the glyoxalase detoxification system. We show that mRNA glycation impairs translation and engages both the integrated stress response and the ribotoxic stress pathway, culminating in compromised pancreatic {beta}-cell function and reduced insulin secretion. Notably, this phenotype is alleviated by the frontline antihyperglycemic agent metformin. Together, our findings position mRNA as a direct sensor of metabolic stress and establish RNA glycation as a mechanistic link between glycolytic imbalance, translational stress and disease.

molecular biology↗

bioRxiv2026

Dual-view Guided Context-aware Network for Automated Bone Lesion Segmentation and Quantification in Whole-body SPECT

Whole-body SPECT bone scintigraphy reflects skeletal metabolic activity throughout the body and plays an indispensable role in the screening, treatment evaluation, and prognostic assessment of bone metastases in tumors. However, the automatic detection and segmentation of hypermetabolic bone lesions remain challenging due to low contrast, limited spatial resolution, and complex lesion distributions. In this study, we proposed Bone-Segnet, a dual-view guided automatic segmentation network for hypermetabolic bone lesions that integrated multi-scale feature modeling, global context modeling, and view-conditioned modulation. Pixel-level annotated anterior and posterior whole-body bone scintigraphy images were used for model training and prediction. The proposed network enhanced the recognition of low-contrast and small-scale lesions through small-lesion enhancement and multi-scale contextual modeling. A Transformer module was further introduced to strengthen global feature representation, while cross-view collaborative modeling was achieved by incorporating the complementary characteristics of anterior and posterior imaging. Experimental results demonstrated that the proposed method outperformed existing approaches across multiple evaluation metrics, with the Dice score improving from 0.7440 to 0.8750, indicating a substantial improvement in segmentation performance. Further quantitative analysis based on the segmentation results revealed significant differences among disease types in lesion count, pixel burden, and spatial distribution patterns, reflecting the heterogeneity of disease-related skeletal metabolic activity. Overall, the proposed method improved automatic lesion segmentation performance and enabled quantitative analysis of lesion burden and spatial distribution patterns, providing objective data support for the assessment of related diseases. Index Terms--Whole-body SPECT, bone lesion segmentation, dual-view modeling, quantitative analysis.

bioinformatics↗

bioRxiv2026

Stage-specific CHI3L1/YKL-40 signaling controls generation of oligodendrocyte precursor cells through IL13Rα2-mediated ferroptosis

Oligodendrocyte precursor cells (OPCs) are essential for sustaining myelin plasticity and maintaining oligodendroglial homeostasis throughout life. However, the intrinsic signaling mechanisms that regulate OPC generation from neural progenitors remain incompletely understood. Here, we identify chitinase-3-like protein 1 (CHI3L1/YKL-40) as a stage-specific, intrinsic signaling regulator of oligodendroglial lineage progression. Using human iPSC-derived models, we show that CHI3L1 selectively targets a transient IL13R2-expressing pre-OPC population, where it induces ferroptosis through suppression of GPX4, thereby limiting OPC generation. In contrast, CHI3L1 does not trigger cell death in established OPCs but instead suppresses their proliferation and differentiation while promoting a reactive, immune-like transcriptional state. Mechanistically, IL13R2 mediates CHI3L1-dependent ferroptotic vulnerability at the pre-OPC stage, distinguishing it from parallel signaling pathways that regulate neuronal differentiation. Functionally, this dual-stage regulation constrains the production and maintenance of OPCs, a critical determinant of oligodendroglial homeostasis and myelin plasticity. These findings define an intrinsic signaling axis that couples stage-specific cell fate vulnerability to ferroptotic cell death, thereby controlling OPC pool dynamics with broad implications for cognitive function and disorders involving disrupted myelination.

neuroscience↗

bioRxiv2026

Co-expression of IBDV VP2 and H9N2 HA by recombinant HVT induces high protection against both pathogens in chickens

Infectious bursal disease virus (IBDV) and H9N2 avian influenza virus (AIV) are significant global threats to poultry health and production. While IBDV induces severe immunosuppression, undermining host defense and vaccine efficacy, H9N2 AIV is characterized by widespread prevalence, persistent shedding, and substantial economic losses. Conventional inactivated vaccines often fail to elicit robust cellular immunity and necessitate multiple booster doses, underscoring the urgent requirement for advanced multivalent vaccination platforms. To address this, we developed a recombinant herpesvirus of turkey (rHVT BAC-VP2-HA) using a bacterial artificial chromosome (BAC) vector system, engineered to co-express the major protective antigen VP2 of IBDV and the hemagglutinin (HA) of H9N2 AIV. Genetic stability and in vitro characterization confirmed that the recombinant exhibited replication kinetics and plaque morphology comparable to parental HVT, with stable antigen expression. In SPF chickens, rHVT BAC-VP2-HA induced strong humoral immune responses against both target antigens, comparable to those elicited by a commercial inactivated vaccine. Crucially, the recombinant virus significantly enhanced cellular immunity, evidenced by markedly elevated CD3+CD8+ T cell responses. Upon challenge, the recombinant conferred high clinical protection (86%) against virulent IBDV, significantly ameliorating bursal pathology and reducing viral loads. Notably, it provided complete (100%) protection against H9N2 AIV, effectively abolishing viral shedding and suppressing viral replication in respiratory tissues. These results demonstrate that rHVT BAC-VP2-HA is a safe and efficacious candidate capable of eliciting humoral and cellular immune responses, offering a promising strategy for the integrated control of major poultry diseases. ImportanceInfectious bursal disease virus (IBDV) and H9N2 avian influenza virus (AIV) are major pathogens that frequently co-circulate in poultry, where IBDV-induced immunosuppression compromises the efficacy of vaccination against other infectious diseases. Conventional inactivated vaccines primarily induce humoral immunity and are often insufficient to prevent viral shedding or provide broad protection against multiple pathogens. In this study, we developed a recombinant herpesvirus of turkeys (HVT) vaccine co-expressing the IBDV VP2 and H9N2 HA antigens and demonstrated that it induces both robust antibody responses and enhanced CD8+ T cell immunity. Notably, this vaccine not only provided effective protection against IBDV but also completely prevented viral shedding following H9N2 challenge. These findings highlight the advantage of HVT-vectored multivalent vaccines in eliciting balanced immune responses and controlling virus transmission, providing important insights for the development of next-generation vaccines against immunosuppressive and respiratory viral co-infections in poultry.

microbiology↗

bioRxiv2026

Multi-factorial regulatory networks of placental antibody transfer by Fc receptors and maternal IgG Fc characteristics are modulated by clinical covariate profiles

Maternal immunoglobulin G (IgG) transferred across the placenta is crucial for newborn immunity. IgG transfer efficiency modulated by Fc characteristics including subclass and glycosylation gives rise to diverse transfer profiles across the population, yet the molecular mechanisms driving this variation are incompletely understood. To disentangle multimodal molecular relationships driving population heterogeneity in maternal-fetal antibody transfer, we characterized placental and serological antibody features in matched human tissues from two geographically distinct cohorts. Unsupervised clustering of maternal clinical covariates in both cohorts revealed a distinct patient profile with reduced plasma C-reactive protein and pregravid BMI and enhanced transfer efficiency of IgG subclasses. Quantification of IgG Fc glycan structures in matched maternal and cord plasma by liquid chromatography-mass spectrometry revealed subclass-specific IgG glycosylation patterns which impacted placental transfer efficiency and correlated with these key clinical features. We profiled expression and colocalization of key Fc {gamma} Receptors (Fc{gamma}Rs) by multiplex immunohistochemistry, revealing cell type-specific expression patterns. Variable Fc{gamma}R expression across gestation was consistent in both cohorts, implicating Fc{gamma}Rs as key drivers of temporal antibody transfer dynamics. While Fc{gamma}Rs were not strongly variable across the clinical profiles, partial correlation analysis of matched samples controlling for gestational age and demographic covariates revealed correlations between Fc{gamma}R expression frequencies and glycan- and subclass-specific transfer efficiency. These data systematically define multi-factorial regulatory networks of antibody transfer by placental Fc receptors and maternal IgG Fc characteristics, which are further modulated by clinical covariates. This study provides a basis for the rational design of prenatal vaccination strategies, administration schedules, and potential lifestyle interventions to improve maternal-fetal immunity.

immunology↗

bioRxiv2026

PromptBio-Bench: Benchmarking LLM-based Bioinformatics Agents for End-to-End Data Analysis

Large language model (LLM)-based agents hold transformative potential for automating bioinformatics workflows; however, systematic evaluations of their capabilities remain limited, hindering a clear assessment of their readiness for real-world application. We introduce PromptBio-Bench, a comprehensive evaluation suite of 244 expert-curated tasks spanning bioinformatics and data science at varied difficulty levels, and an evaluation framework for structured file comparison and scoring against expert reference answer files. Evaluation of three state-of-the-art bioinformatics agents revealed comparable performance between Biomni and ToolsGenie, with all agents showing a marked decline in accuracy as task difficulty increased. As foundation models and agent frameworks continue to evolve, PromptBio-Bench provides a valuable benchmark infrastructure for systematically tracking progress in agentic bioinformatics.

bioinformatics↗

bioRxiv2026

A natural soil-derived microbiota reshapes nitrogen form and plant mineral nutrition

Nitrogen form in soil has a major influence on plant growth and mineral nutrition, yet whether and how nitrogen form is controlled by microbiota in natural soils remains poorly understood. Here we show that, in a high-organic-matter soil from Danish nature, the native soil microbiota determines nitrogen form and thereby controls plant mineral nutrition. Eliminating the microbiota by sterilization disrupted nitrification, causing ammonium accumulation and loss of nitrate, which resulted in impaired growth and a pronounced reduction in shoot Mg and Ca associated with chlorosis. Reintroduction of a simplified soil-derived microbiota restored nitrification and re-established a balanced NO{square}{square}/NH{square}{square} regime, which rescued Mg and Ca accumulation, alleviated chlorosis, and promoted plant growth. Metagenomic analyses of bulk soil, rhizosphere, and root-associated communities revealed enrichment of nitrogen-cycling functions, including nitrification-related genes, supporting the capacity of the restored microbiota to modulate nitrogen form in soil and the rhizosphere. Moreover, this microbiota alleviated mineral deficiency symptoms in an organic agricultural soil. Together, our findings reveal a natural microbiota-dependent mechanism by which soil microbes determine nitrogen form and thereby regulate plant mineral nutrition, particularly Mg and Ca homeostasis.

plant biology↗

bioRxiv2026

Microglial pruning of extinction-ensemble synapses preserves fear memory

Fear extinction suppresses learned fear without erasing the original memory, yet how competing fear and extinction ensembles are selectively updated remains unknown. Here, we show that microglia preserve fear memory by selectively editing extinction-ensemble synapses during retrieval. In medial prefrontal cortex, microglial processes, but not somata, expand, ramify, and tighten their engagement with extinction-ensemble dendrites and spines, where they preferentially engulf excitatory postsynaptic material and bias spine remodeling toward elimination. This selectivity is instructed by local find-me, eat-me, and dont-eat-me cues: purinergic signaling recruits microglial processes, phosphatidylserine exposure licenses engulfment of extinction-ensemble synapses, and CD47-SIRP protects fear ensembles from removal. Weakening microglial recruitment or engulfment, or removing this protection, accelerates extinction without impairing fear acquisition. These findings identify microglial processes as active gatekeepers of ensemble competition and reveal a neuroimmune mechanism that preserves fear memory by limiting extinction. In BriefDuring memory updating, microglial processes selectively engage extinction-ensemble synapses rather than globally pruning active circuits. Local recruitment, engulfment, and protection cues determine this choice, allowing microglia to preserve fear memory by limiting extinction. HighlightsO_LIExtinction retrieval selectively recruits microglial processes to extinction ensembles. C_LIO_LIMicroglia preferentially engulf excitatory postsynaptic material from extinction ensembles. C_LIO_LILocal "find-me," "eat-me," and "dont-eat-me" cues determine synapse selection. C_LIO_LIDisrupting microglial pruning facilitates extinction without impairing fear learning. C_LI

neuroscience↗

bioRxiv2026

An ancient cis-element regulates translation of arginine decarboxylase to control downstream polyamine biosynthesis and stress responses

Polyamines (PAs) are ubiquitous metabolites that, despite their simple structure, profoundly influence plant growth, development, and stress adaptation. Their cellular levels are largely determined by arginine decarboxylase (ADC), a key rate-limiting enzyme in their biosynthesis. We previously identified a [~]50 bp GC-rich sequence in the 5' untranslated region (UTR) of plant ADC genes, termed the ADC-box, that is conserved across land plants. Transient reporter assays in tomato, in which ADC upstream regions were decoupled from their native coding sequences and fused to reporter genes, suggested that this element represses translation. However, its function in the native genomic context and its impact on PA homeostasis remain unclear. Here, we combined CRISPR-Cas9 genome editing, metabolite profiling, enzymatic assays, and RNA structure probing to define ADC-box function in tomato and in the seedless land plant Marchantia polymorpha, which retains a conserved [~]20 bp core region. Mutation of the M. polymorpha ADC-box increased ADC activity and altered PA levels, indicating that the ADC-box functions as a conserved translational repressor. In tomato, disruption of the ADC-boxes in SlADC1 and SlADC2 increased ADC activity, demonstrating that the ADC-box acts as a translational repressor in its native context. These ehects were most pronounced under cold stress, when ADC transcript levels increase, suggesting that the ADC-box buhers stress-induced translation. Metabolically, ADC-box disruption led to agmatine accumulation and alterations in upstream intermediates, while downstream PA pools remained largely unchanged. SHAPE analysis revealed that the tomato ADC-box folds into a three-stem RNA structure, with a central stem representing the major inhibitory module. ADC-box mutants displayed altered plant-microbe interactions, with enhanced resistance to Pseudomonas syringae and Tobacco rattle virus, but increased susceptibility to Ralstonia solanacearum and Tomato yellow leaf curl virus. Together, these findings establish the ADC-box as an evolutionarily conserved cis-regulatory element that stabilizes PA homeostasis and modulates plant-microbe interactions.

plant biology↗

bioRxiv2026

Increased Telomere Mobility in Progeria is Restored by Isoprenylcysteine Carboxyl Methyltransferase Inhibition

Hutchinson-Gilford Progeria Syndrome (HGPS) is a genetic disease characterized by the accumulation of progerin, a mutant form of lamin A, at the nuclear envelope. Progerin disrupts the stability of the nuclear lamina, leading to genome instability and accelerated aging phenotypes. While structural nuclear defects are well-documented, the impact of progerin on real-time chromatin dynamics and the ability of current therapeutics to rescue these dynamics remains poorly understood. In this work, we employ single-particle tracking to quantify telomere dynamics in HGPS patient fibroblasts. We demonstrate that HGPS cells exhibit significantly increased telomere dynamics, characterized by expanded scan areas, increased diffusion coefficients, and larger jump distances compared to healthy controls. We further evaluated the efficacy of two clinically relevant treatments, the farnesyltransferase inhibitor Lonafarnib and the ICMT inhibitor C75, to determine if emerging treatments can restore chromatin dynamics compared to healthy controls. Our results reveal that Lonafarnib partially rescues telomere dynamics, shifting chromatin motion back towards healthy control levels, and that C75 provides a complete rescue of the dynamics for all parameters quantified. These findings provide a quantitative framework for understanding how nuclear lamina mutations induce aberrant genome dynamics and the efficacy of HGPS therapies on restoring those dynamics.

biophysics↗

bioRxiv2026

Dysregulated tissue-resident lymphocytes drive age-associated emphysema by impairing alveolar regeneration

Aging is often associated with progressive tissue degeneration and chronic inflammation, yet the role of immune cells in mediating structural and functional decline in organs remains poorly defined. Here, we investigated immune-tissue interactions in the aged lung and identified emphysematous remodeling characterized by alveolar loss. Notably, aged lungs exhibited a marked expansion of tissue-resident lymphocytes (TRLs) with senescent features, accompanied by a significant reduction in alveolar stem/progenitor cell (AT2) abundance. In vivo adoptive T cell transfer and 3D immune-stem cell organoid assays revealed that these expanded TRLs suppressed AT2 growth via secretion of oncostatin M and interferon gamma. In vivo blockade of IL-7 receptor (IL-7R) reduced TRL accumulation in the lungs and ameliorated age-related emphysematous changes, including restoration of alveolar density. Our findings identify TRLs as key drivers of alveolar degeneration in aging and propose IL-7R inhibition as a therapeutic strategy to mitigate pulmonary decline. TeaserBlocking IL-7R clears harmful lymphocytes and helps rebuild the damaged air sacs of the aging lung.

cell biology↗

bioRxiv2026

Posterior parietal cortex guides sensorimotor associative learning by linking sensation to distal action

Sensorimotor associative learning is challenged when sensory cues and motor responses are separated by a delay, limiting the coactivity required for Hebbian plasticity. Here we identify the rostro-lateral posterior parietal cortex (PPC-rl) as a cortical hub that bridges tactile stimuli and delayed licking during learning. Using cortex-wide calcium imaging with single-cell resolution to track ~16,000 neurons simultaneously across sensory, motor, and association cortices, we find that PPC-rl exhibits sustained delay-epoch activity early in learning that diminishes with expertise. Optogenetic silencing slows learning without impairing expert motor execution. Learning strengthens intra- and inter-areal sensorimotor coupling, and PPC-rl mediates this process by amplifying a low-dimensional communication subspace that aligns sensorimotor co-fluctuations. A biologically plausible network model shows that PPC-rl persistence, subspace alignment, and reward-gated Hebbian plasticity synergize to support delayed association. These findings uncover a PPC-rl based cortical mechanism that maintains temporal continuity to link sensation with distal action during learning.

neuroscience↗