Biology subjects

Lin, F.

Publications and source records attributed to Lin, F..

At least 19 recordsLinked to original sources

bioRxiv2026

Sperm development requires TMC5-dependent mechanoresponsive calcium entry

Spermiogenesis, the transformation of round spermatids into streamlined, fertilization-competent sperm, represents cellular morphogenesis at its most extreme. Despite decades of effort, spermiogenesis remains difficult to recapitulate outside the testis, highlighting the importance of cues within the native tissue environment. The nature of these cues, however, remains poorly understood. Here, we discover that mechanical stimulation elicits Ca2+ entry in spermatids and identify transmembrane channel-like protein 5 (TMC5) as a principal mediator of this response. In both mouse and human testes, TMC5 is selectively expressed in spermatids and localized to the plasma membrane. TMC5 associates with TMC7 and calcium- and integrin-binding (CIB) proteins, mirroring TMC-CIB mechanotransduction complexes in sensory organs. Mechanistically, loss of Tmc5 blocks mechanically evoked Ca2+ entry, leading to disruptions in cytoskeletal remodeling and failure of CREM [&tau] dependent transcriptional programs required for spermiogenesis. Thus, TMC5 is required to couple mechanical cues to sperm development, with direct implications for male infertility.

cell biology↗

bioRxiv2026

A Hymenoptera-restricted gene mediating ant castes co-opts deeply conserved machinery to control organ size

Lineage-specific genes are widespread and have been implicated as phenotypic innovation inducers, but how they acquire complex developmental functions remains poorly understood. Ant queens and workers develop dramatically different organ sizes from identical genomes under juvenile hormone (JH) control, yet the molecular effectors translating JH signalling into caste-specific organ growth remain unknown. Here we identify torch, a Hymenoptera-restricted gene, as the most consistently gyne-biased and JH-responsive gene across 68 ant species. Knockdown of torch in virgin queens of Monomorium pharaonis produces a worker-like, multi-organ growth-restricted phenotype. Mechanistically, torch harbours an E-box-like motif activated by the JH receptor Gce-Tai and acts as a GA-repeat-binding transcription factor that regulates Hippo signalling, the deeply conserved organ-size control pathway in animals. Expressing torch heterologously in mice and a growth-restricted Drosophila background shows that the gene retained its general growth-promoting activity across more than 700 million years of animal evolution in lineages that lack the gene, establishing that its function is mediated through conserved rather than ant-specific machinery. A lineage-specific gene can therefore acquire complex morphogenetic function by co-opting ancient organ-size circuitry, providing a general route by which novel genes can drive phenotypic innovation.

evolutionary biology↗

bioRxiv2026

A patient-centric therapeutic paradigm uncouples prostate cancer suppression from systemic metabolic collapse

The clinical benefits of cancer therapies are often compromised by the tolerable adverse effects that impair systemic organismal health and may evolve into latent life threats. Here, we identified profound abiraterone-induced but androgen-independent metabolic perturbations in prostate cancer patients and developed Lifehug-9892 to balance tumor therapy with systemic metabolic homeostasis. By integrating population cohorts with high-resolution metabolomics, we demonstrate that abiraterone induces profound systemic lipidomic dysregulation, characterized by the massive, pathological accumulation of desmosterol. Abiraterone inhibits but stabilizes DHCR24, leading to a metabolic trap in patients showing elevated levels of both desmosterol and cholesterol. Desmosterol accumulation is highly lipotoxic, potently triggering endothelial cell senescence and necrosis, macrophage foam cell formation, murine atherosclerosis, and hepatic senescence. To mechanistically uncouple and therapeutically rescue this systemic metabolic collapse, Lifehug-9892 was rationally designed to selectively retain on-target CYP17A1 inhibition while completely sparing DHCR24 function. Lifehug-9892 maintains potent tumor-suppressive activity while fully preserving the desmosterol-cholesterol metabolic axis and preventing systemic cardiovascular and hepatic damage. Our study uncovers a critical mechanistic link between drug-induced metabolic dysregulation and organismal health in cancer patients, providing a biochemical framework for developing patient-centric targeted therapies that preserve host homeostasis.

cancer biology↗

bioRxiv2026

Genic Position and Methylation Context Shape DNA Methylation-Expression Relationships in Rice Internode Development

Elongating rice internodes present a developmental gradient from dividing meristem to mature cells, providing an elegant pseudo-time course for study of plant vegetative development. We tested the hypothesis that DNA methylation regulates gene expression during rice internode development by integrating RNA-seq and bisulfite DNA sequencing across eight internode segments. Previously described topologically associated chromatin domain borders aligned with transcription start sites of constitutive expressed genes. CpG and CHG differential methylation was enriched in young segments, consistent with maintenance methylation; whereas CHH methylation showed similar differential abundance in young and old segments. CHH and CHG methylation in upstream regions, CpG methylation within gene bodies, and any methylation in 5' and 3' untranslated regions were permissive of moderate to high gene expression. Very low expression was associated with CpG methylation upstream, CHG and CHH methylation within gene bodies, and CpG and CHG methylation downstream. A nonrandom subset of genes, including cell wall-related glycoside hydrolases, lignin and tricin biosynthesis enzymes, and WD40 proteins, showed methylation-expression correlations, with expression changes enriched in triple-marked elements. These results suggest that internode phenotypes of DNA methylation machinery mutants relate to alteration of specific target genes, opening approaches for grass culm improvement for lodging resistance and biomass production. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/737558v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@b726eaorg.highwire.dtl.DTLVardef@5bd017org.highwire.dtl.DTLVardef@1bac873org.highwire.dtl.DTLVardef@1be3474_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance statementStems of cereals and other grasses have an important function in supporting grain production and serving as a source of carbon for the bioeconomy. This study supports methylation of the cytosine bases of DNA as a regulator of chromatin structure and gene expression in the stems of rice. Different methylation contexts are implicated in specific roles in both positive and negative gene expression regulation that might be leveraged to improve stem properties.

plant biology↗

bioRxiv2026

Targeting ALA3 with propiconazole regulates plant growth and enables discovery of promising inhibitor leads

Propiconazole (PCZ) is widely misused growth regulator in leafy Brassica vegetables. Developing green strategies for managing plant architecture has become an urgent agricultural priority. Here, we identified from a membrane-protein-defective yeast library a P4-ATP phospholipid flippase, aminophospholipid ATPase 3 (ALA3), as a target sensitive to PCZ. ALA3 exhibits high binding affinity for PCZ, which inhibits its ATPase activity. Knockdown of ALA3 rendered yeast, Arabidopsis, and Brassica rapa less sensitive to PCZ and conferred a growth-inhibited phenotype. This dwarfing phenotype is mediated through the interaction between ALA3 and CYP51G1 that jointly acts within the brassinosteroid regulatory pathway. Furthermore, we identified lead compounds A01 and A15 as ALA3-targeting agents, and compared to PCZ, they display superior binding affinity and reduced toxicity. Our work establishes ALA3 as a key mediator of PCZ-induced dwarfism and provides dual strategies--creating promising varieties through gene editing and developing targeted green pesticides--to reduce PCZ use. TeaserTargeting ALA3 reduces PCZ use through gene-edited varieties and green pesticides.

plant biology↗

bioRxiv2026

The BraALA3 Homologs Mediate Propiconazole-Modulated Plant Growth in flowering Chinese cabbage

In agriculture, propiconazole (PCZ) controls excessive growth in flowering Chinese cabbage but poses dietary safety risks due to residue accumulation. Therefore, identifying novel PCZ targets and breeding PCZ-free cultivars is critical for the safe production of flowering Chinese cabbage. Here, we identified three P4-ATPase flippase homologs aminophospholipid ATPase 3 (BraALA3a/b/c) in flowering Chinese cabbage that function as sensitive targets for PCZ. These proteins exhibit high binding affinity for PCZ, which directly inhibits their ATPase activity. Overexpression of the BraALA3 homologs enhanced plant growth and increased sensitivity to PCZ, whereas knockdown led to dwarfism and reduced sensitivity. Based on these findings, we identified editable active sites via protoplast-based screening. Genetic transformation of one such site yielded BraALA3a/braala3aK200T mutant lines, which displayed a dwarf and compact architecture. These findings provide a precise molecular target for developing PCZ-free germplasm in flowering Chinese cabbage through gene editing.

plant biology↗

bioRxiv2026

Mouse Predation is Dependent on a Population of POU6F2-Positive Retinal Ganglion Cells

The contribution of retinal ganglion cells (RGCs) subtypes to visually guided behavior continues to be an active area of research. We identify POU6F2-expressing RGCs essential for binocular predatory behavior. The POU6F2 RGCs are ON-OFF direction-selective RGCs that are vulnerable to glaucomatous injury. In Pou6f2 knockout (Pou6f2-/-) mice, there is a 12% loss of RGCs, and these cells are the POU6F2-expressing RGCs. Functionally, Pou6f2-/-mice exhibited profound deficits in contrast sensitivity. In this study we found a deficit in the ability of Pou6f2-/- mice to perform a binocularly driven cricked predation test. Wildtype mice detect and capture the cricket rapidly; while, both Pou6f2-/- mice and mice with one optic nerve crushed, required significant longer times to complete the task. After optic nerve crush no further impairment in performance is seen in the knockout mouse. These data demonstrate that the POU6F2-positive RGCs are essential for this binocularly driven behavior.

neuroscience↗

bioRxiv2026

lncRNAs contribute to caste differentiation as a regulatory layer in ants

Caste differentiation in ants represents one of the major evolutionary transitions and provides a unique model for studying developmental mechanisms underlying division of labor. Genetically identical individuals follow divergent epigenetically-regulated developmental trajectories that give rise to morphologically distinct phenotypes and specialized roles. While long non-coding RNAs (lncRNAs) are emerging as key epigenetic regulators across diverse biological systems, their specific contributions to caste development in social insects remain largely unexplored. Here, we conducted comprehensive transcriptomic analyses across major developmental stages of two evolutionarily and ecologically distinct ants Monomorium pharaonis and Acromyrmex echinatior, identifying over 10,000 lncRNAs. We demonstrated that lncRNAs exhibit dynamic, caste-specific expression patterns throughout development. We also identified a subset of lncRNAs displaying canalized expression patterns, characterized by progressively increasing caste bias and decreasing within-caste variation as development proceeds. Co-expression analyses revealed that canalized lncRNAs are functionally linked to canalized protein-coding genes, which are crucial regulators for caste differentiation. These canalized lncRNAs show striking tissue-specific enrichment consistent with canalized protein-coding genes. Functional validation through RNA interference revealed that canalized lncRNAs directly regulate caste-specific traits. Furthermore, juvenile hormone treatment capable of redirecting worker lncRNA expression profiles toward gyne-like patterns, with similar expression changes and tissue specificity to JH-responsive protein-coding genes, linking lncRNA regulation to established hormonal pathways controlling caste fate. Our findings establish lncRNAs as active architects of caste differentiation in social insects, demonstrating that these rapidly-evolving regulatory molecules contribute to the evolution and maintenance of social phenotypes through tissue-specific regulation of caste-associated developmental programs.

developmental biology↗

bioRxiv2025

GENET: AI-Powered Interactive Visualization Workflows to Explore Biomedical Entity Networks

Formulating hypotheses about gene-disease associations requires logical inference from prior data, followed by a laborious literature review. AI models trained on curated datasets (e.g., GWAS Catalog) can suggest SNP-disease links, but validating these predictions still demands manual evidence extraction. To streamline this process, we present GENET (Genomic Evidence Network Exploration Tool), an AI-enhanced, end-to-end visual analytics workflow applied to Age-Related Macular Degeneration (AMD). GENET comprises four sequential steps: (1) biomedical network analysis: a dual-encoder neural model identifies genes or SNPs associated with a target disease and vice versa; (2) literature evidence mining pipeline: a pipeline retrieves relevant papers and, using large language models, extracts biomedical entities and relations; (3) clustering: embeddings from pre-trained biomedical language models (BioBERT, BioLinkBERT) are clustered to group related concepts; (4) interactive visualizations: clusters and their networks are visualized with interactive features for hypothesis testing and insight generation. The workflow enables iterative hypothesis formulation and evidence validation, uncovering novel associations. GENET is open-sourced (https://github.com/BiomedSciAI/genet) and available for demonstration at https://genet.pythonanywhere.com.

bioinformatics↗

bioRxiv2025

The FERM Guild: A Differentially Correlated Microbial Module Drives Hypertension via Metabolic Flux Perturbations

BackgroundHypertension is a major risk factor for cardiovascular diseases, with changes in gut microbiota composition and function being closely associated with its onset and progression. However, the high inter-individual variability in gut microbiota complicates the identification of pathogenic mechanisms using traditional methods. In contrast, the smaller variability in gut microbial metabolites offers a more reliable and consistent basis for cross-individual comparisons. ResultsParsimonious Flux Balance Analysis (pFBA), integrated with Double Machine Learning (DoubleML), identified 17 metabolites significantly associated with hypertension (p < 0.05, RobustnessV alue > 0.1). These included meso-2,6-diaminoheptanedioate, p-hydroxyphenylacetic acid, cellobiose, dextran 40 (1,6--D-glucan), L-glutamic acid, kestopentaose, among others. Differential microbial correlation network analysis identified a key microbial sub-network, the FERM guild, consisting of 19 species, with prominent genera including Faecalibacterium,Enterobacter,Roseburia, and Methanobrevibacter. Using GSEA, the dysregulation of this guild was found to be strongly associated with a set of 17 hypertension-related metabolites(p = 0.017). Further analysis revealed that the contribution of FERM genus to key metabolites is significantly associated with blood pressure (p < 0.05), even without significant differences in their abundance; additionally, an imbalance exists between FERM genus and other species. ConclusionsOur findings reveal that hypertension is associated with a disruption of gut microbial diversity, structure, and metabolic function. Seventeen key metabolites related to blood pressure regulation were identified, exhibiting pro- or anti-hypertensive potential and linked to functional microbial modules. These results highlight the gut microbiota and its metabolites as promising targets for therapeutic intervention in hypertension.

bioinformatics↗

bioRxiv2025

Exploring Stress-Induced Neural Circuit Remodeling through Data-Driven Analysis and Artificial Neural Network Simulation

Chronic stress is associated with alterations in neural circuit dynamics, yet the computational principles underlying these changes remain incompletely understood. Here, we reanalyzed in vivo GCaMP8s recordings from BLA-DMS and CeA-DMS projection pathways using three complementary descriptive approaches. First, Kullback-Leibler (KL) divergence was used to quantify stress-related changes in activity distributions, revealing context-dependent alterations in population-level neural responses. Second, a phenomenological second-order regression framework was employed to characterize local recovery-related dynamical features, providing a compact descriptive representation of pathway activity without implying mechanistic identification. Third, a simplified artificial neural network (ANN) was implemented as a hypothesis-generating sufficiency test. Under asymmetric optimization constraints, the model generated response profiles qualitatively resembling selected features observed experimentally. Robustness analyses indicated that similar qualitative behaviors emerged across multiple parameter initializations. Together, these results provide a multi-level descriptive characterization of stress-associated neural activity alterations across statistical, dynamical, and computational representations, while explicitly avoiding assumptions of a unified mechanistic mapping between analytical levels.

neuroscience↗

bioRxiv2025

Estrogen Dependent Variation in the Contributions of TRPM4 and TRPM5 to Fat Taste

Sex differences in physiology have garnered significant interest of late; however, comparatively little is known about the effects of sex on the function of the peripheral taste system. Previously, we have shown that fat taste functions in a sexually dimorphic manner using molecular, cellular, and behavioral assays, and that a subtype of estrogen receptor (ER) proteins are highly expressed in Type II (receptor) cells. The underlying mechanisms of estrogens action, though, remain unknown. Here, we sought to better understand estrogens role in fat taste transduction at the molecular level by initially focusing on the transient receptor potential channels types M4 (Trpm4) and M5 (Trpm5), which we have shown to play roles in estrogen-sensitive fatty acid signaling in taste cells. That is, using Trpm5-deficient mice, both males and females in the estrus phase showed significantly reduced FA responses, whereas females in the proestrus phase did not, suggesting that there may be E2-dependent TRPM5-independent FA signaling in Type II cells. During periods of high levels of circulating estrogen, there was no significant difference in cellular responses to fatty acid (FA) stimuli between Trpm5-/- mice and their wild-type counterparts. Moreover, supplemental estradiol enhanced linoleic acid (LA)-induced TRPM5- mediated taste cell activation. Finally, while Type II cells depend on TRPM4 and TRPM5 for FA taste cell activation, proestrus (high estrogen) females showed a greater dependence on a TRPM5-independent pathway for fatty acid responsiveness. Together, these results underscore the substantial regulatory role of estrogen in the taste system, particularly for fatty acid signaling. Given that the taste system guides food preferences and intake, these findings may have important implications for understanding sex-specific differences in diet and, ultimately, metabolic health. SUMMARYThe current manuscript shows sex differences in fat taste signaling and identifies functional variations in specific transduction elements in taste cells that respond to sex hormones, such as estrogen, that may mediate differences in peripheral fat taste pathways.

neuroscience↗

bioRxiv2025

Beyond reference bias: Making pangenomes accessible with PangyPlot

Linear reference genomes have standardized genomics research but remain limited by reference bias, which skews read mapping and variant discovery. This bias can distort the interpretation of genetic variation, particularly for populations that are genetically distant from the reference. Pangenome graphs, such as those generated by the Human Pangenome Reference Consortium (HPRC), mitigate this limitation by integrating diverse haplotypes into a unified representation of human genetic variation. However, the complexity of graph-based data and the lack of intuitive visualization tools have hindered broader adoption. Here we introduce PangyPlot, a genome browser that simplifies exploration of pangenome graphs by retaining linear-style navigation, integrating gene annotations, abstracting complex variation into interpretable structures, and employing a dynamic, physics-based layout optimization engine. We demonstrate its utility by constructing a chromosome 7 graph from 101 individuals with cystic fibrosis (CF), capturing a broad spectrum of genetic variation. Using PangyPlot, we visualized CF-relevant loci and compared results with existing graph viewers, highlighting its ability to display both base-level and large structural variation. With an additional 64 PacBio HiFi assemblies, we fine-mapped a repeat-dense CF modifier locus on chromosome 5, where PangyPlot was used in conjunction with graph-based analysis to identify a repeat expansion in the 5' end of EXOC3 that may promote G-quadruplex formation and affect gene expression. Together, these examples demonstrate PangyPlot s capacity to make populationlevel variation interpretable. To support broader use of graph-based resources, we also released a live public instance of PangyPlot preloaded with HPRC data (https://pangyplot.research.sickkids.ca/).

genomics↗

bioRxiv2025

Single-Cell RNA and ATAC Sequencing Reveal Cellular Heterogeneity and Chromatin Accessibility Dynamics in Young Chinese Breast Cancer Patients across Pre- and Post-Neoadjuvant Therapy

Young breast cancer (YBC) patients (age [≤] 40) exhibit aggressive features and poor prognosis, while facing complex needs including breast-conserving surgery and fertility preservation. Neoadjuvant therapy (NAT) is important for tumor downstaging and breast-conserving surgery in YBC treatment, but the NAT response mechanisms in YBC patients remain unelucidated. Here, we analyzed pre- and post-NAT samples from Chinese YBC patients using scRNA-seq and scATAC-seq. We found that NAT reshaped cellular heterogeneity in the tumor microenvironment (TME), reducing epithelial and T cells while increasing endothelial cells and fibroblasts. Residual cancer cells showed enriched epithelial-mesenchymal transition (EMT) and stromal remodeling programs. NAT responders had fewer luminal-like cells and retained basal-like cells in an early hybrid EMT state, whereas non-responders maintained both populations with late hybrid EMT. We identified therapy-resistant genes and motifs (e.g., VTCN1, PROM1, MZB1, Fox family) and linked CXCL13 upregulation to poor NAT response and tumor-specific T-cell expansion. Cell-cell communication analysis revealed NAT reprograms the TME by suppressing VEGF and TNF signaling in basal cells, while residual luminal cells transmit EGFR and CD47-SIRPA signals.

cancer biology↗

bioRxiv2025

GWAS SVatalog: a visualization tool to aid fine-mapping of GWAS loci with structural variations

BackgroundGenome-wide association studies (GWAS) have been successful in identifying single nucleotide polymorphisms (SNPs) associated with phenotypic traits. However, SNPs form an incomplete set of variation across the genome and since a large percentage of GWAS-significant SNPs lie in non-coding regions, their impact on a given trait is difficult to decipher. Recognizing whether these SNPs are tagging other polymorphisms, like structural variations (SV), is an important step towards understanding the putative causal variation at GWAS loci. ResultsHere, we develop GWAS SVatalog (https://svatalog.research.sickkids.ca/), a novel open-source web tool that computes and visualizes linkage disequilibrium (LD) between SVs and GWAS-associated SNPs throughout the human genome. The tool combines GWAS Catalogs SNP-trait association data across 14,479 phenotypes with LD statistics calculated between 35,732 SVs and 116,870 SNPs identified in 101 whole-genome long-read sequences. We use GWAS SVatalog to identify SVs that may explain GWAS loci for iron levels, refractive error, and Alzheimers disease, where previously SNPs were unable to provide a causal explanation. ConclusionsGWAS SVatalog advances the fine-mapping of GWAS loci with structural variations, enabling researchers to associate 35,732 common SVs with 14,479 phenotypes, accelerating the understanding of disease etiology.

bioinformatics↗

bioRxiv2025

The pro-inflammatory cytokines IFN-α and TNF-α inhibit organoid-derived extravillous trophoblast invasion

Proper placental development requires differentiation and invasion of extravillous trophoblasts (EVTs) into the maternal decidua to ensure adequate remodeling of spiral arteries and support fetal growth. Perturbations in these processes are associated with pregnancy complications such as preeclampsia and fetal growth restriction. The incidence of these pregnancy complications is increased in women with immune-mediated inflammatory diseases, which are characterized by elevated levels of pro-inflammatory cytokines, such as interferon alpha (IFN-) and tumor necrosis factor alpha (TNF-). However, the direct effects of these cytokines on trophoblast differentiation and invasion remain unclear. Using human trophoblast organoid models, we demonstrate that IFN- and TNF- impair EVT invasion while preserving their differentiation capacity. High-resolution imaging of untreated organoid-decidua co-cultures revealed extensive invasion of organoid-derived trophoblasts into the decidual stroma and spiral arteries. In contrast, organoids treated with IFN-, in particular, exhibited markedly reduced invasion within this system. Transcriptome profiling indicated altered expression of several pathways involved in invasion upon cytokine treatment. These findings support the notion that elevated levels of IFN- and TNF- can directly impair trophoblast invasive capacity, potentially contributing to suboptimal placental development and adverse pregnancy outcomes in the context of inflammatory disorders.

developmental biology↗

bioRxiv2025

Representation Transfer via Invariant Input-driven Neural Manifolds for Brain-inspired Computations

Domain adaptation is a core challenge for embodied AI deployed in unpredictable, noisy environments. Conventional deep models degrade under domain shifts and require costly retraining. Inspired by biological brains, we propose a modular framework where each module is a recurrent neural network pretrained via a simple, task-agnostic protocol to learn robust, transferable features. This shapes stable yet flexible representations as invariant input-driven continuous attractor manifolds embedded in high-dimensional latent space, supporting robust transfer and resilience to noise. At deployment, only a lightweight adapter needs training, enabling rapid few-shot adaptation. Evaluated on the DVS Gesture benchmark and a custom RGB rehabilitation dataset, our framework matches or surpasses leading C3D and ViViT models while using ten times fewer parameters and only one training epoch. By unifying biologically inspired attractor dynamics with cortical-like modular composition, our approach offers a practical path toward robust, continual adaptation for real-world embodied AI. TeaserInvariant input-driven attractors enable representation transfer and domain adaptation in brain-inspired AI.

neuroscience↗

bioRxiv2025

Vascularized Bioengineered Kidney Using Decellularized Scaffold Recellularized with human Placenta-Derived Angiogenic stem Cells and Kidney Organoids

A bioengineered kidney using a decellularized kidney scaffold (DKS) offers a promising solution to the kidney shortage. However, the transplantation of bioengineered kidneys using DKS recellularized with human endothelial, renal cells or others has not yet successfully achieved the vascular and renal reconstruction in vivo. In this study, we identified another type of stem cells, designated as human placenta-derived angiogenic stem cells (hPASCs), which serve as seeding cells for the vascularization of DKS. These hPASCs encompass angiogenic subpopulations, exhibit both stem cell properties and the capacity for vascular differentiation. Human fetal kidney organoids (KIO) were established as a source of renal parenchymal cells, comprising renal, immune, and vascular cell populations. We developed a vascularized bioengineered kidney by recellularizing DKS with hPASCs and KIO using a circulation perfusion culture system. The hPASCs bioengineered kidney demonstrated enhanced angiogenesis and reconstructed renal architecture in vivo, by transplantation into rat models of renal subcapsular and partial nephrectomy. Furthermore, immunofluorescence and single-cell analyses revealed that the hPASCs revascularized bioengineered kidney regenerated both vascular and renal parenchymal cells within the host. This study offers another strategy for kidney bioengineering and regeneration.

bioengineering↗