Biology subjects

Jian, J.

Publications and source records attributed to Jian, J..

12 recordsLinked to original sources

bioRxiv2026

An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid

The retinal pigment epithelium and choroid are critical for supporting the function and maintaining the homeostasis of the outer retina, and their dysfunction underlies a range of inherited and complex ocular diseases. To comprehensively characterize the cellular, transcriptomic, and epigenomic heterogeneity and dynamics within these tissues, we assembled an integrated multi-omics reference atlas comprising 719,813 single-cell/single-nucleus transcriptomes and 234,007 snATAC-seq profiles from 102 ancestrally diverse donors spanning 0 to 99 years of age, including cells from both the macula and periphery. This atlas resolves 48 distinct cell types or states and catalogs 448,567 open chromatin regions. Specifically, we resolved five distinct RPE subpopulations organized along a central-to-peripheral spatial axis, alongside two distinct stress/senescence states. We reconstructed the transcriptomic and epigenetic zonation of endothelial cells and expanded choroidal stromal heterogeneity by characterizing 11 fibroblast and two pericyte types. Age-associated compositional analysis revealed a significant fractional depletion of melanocytes, PI16+ fibroblasts, and venule endothelial cells with age, alongside a modest relative loss of central RPE and a corresponding increase in far-peripheral RPE. Cell-type-specific aging transcriptomics uncovered shared pathways related to inflammatory responses alongside distinct cell-type-specific signatures. Notably, significant age-associated epigenetic changes concentrated in the macula during the transition from early-to-middle adulthood and remained stable into old age, with transcription factors from the AP-1/bZIP family emerging as the dominant enriched motifs. Finally, integrating this atlas with AMD GWAS data provides novel variant-to-gene evidence implicating LIPG and COL4A3 in AMD pathogenesis. Together, this multi-omics atlas serves as both an invaluable community reference and a powerful discovery engine that translates genetic risk signals into localized target cells and candidate mechanisms, laying a foundation for understanding RPE/choroid biology in health and disease.

genomics↗

bioRxiv2026

Chromosome-level genome assembly of Calotes wangi with dynamic colour variation

The Wangs garden lizard, Calotes wangi, is a widely distributed agamid species in Southern China and Northern Vietnam and exhibits pronounced colour variation and rapid body colour change. Despite increasing interest in the genomic basis of colour variation, chromosome-level genomic resources remain limited in agamid lizards. Here, we generated a chromosome-level reference genome of C. wangi using PacBio HiFi sequencing and Hi-C scaffolding. The final genome assembly was approximately 1.66 Gb in size and comprised 6 macrochromosomes and 11 microchromosomes, with a contig N50 of 110.09 Mb and 98.9% complete BUSCO genes. A total of 20,442 protein-coding genes were annotated. Comparative genomic analyses identified 297 significantly expanded gene families, with enriched functions associated with steroid metabolism, chromatin regulation, and epigenetic processes. This high-quality genome assembly provides an important genomic resource for future studies of colour variation, phenotypic plasticity, and evolutionary diversification in agamid lizards.

evolutionary biology↗

bioRxiv2026

An Integrated muti-omics cell atlas of the human trabecular meshwork and ciliary body

The trabecular meshwork (TM) and ciliary body (CB) regulate aqueous humor dynamics and intraocular pressure (IOP), and TM/Schlemms canal (SC) dysfunction underlies glaucoma. Here, we present a spatially resolved multi-omics atlas of human TM and CB, integrating snRNA-seq, scRNA-seq, and snATAC-seq from over one million cells and nuclei across 112 donors with Xenium spatial transcriptomics. We identified 9 major cell classes and 21 cell types, revealing heterogeneity, including undercharacterized fibroblast and epithelial subpopulations. Spatial mapping supported TM fibroblast zonation and CB epithelial organization. Regulatory analyses identified cell type-specific programs, including OTX/PAX networks in CB epithelium and SMAD3/TGF-{beta} signaling in fibroblasts. Integration with glaucoma loci showed enrichment of non-coding variants in regulatory elements associated with POAG and PACG. Age- and ancestry-associated remodeling revealed divergent fibroblast aging with increased PIEZO1, suggesting impaired outflow and elevated IOP. Together, this high-resolution atlas links cellular, regulatory, and genetic variation to anterior segment function and glaucoma susceptibility.

genomics↗

bioRxiv2026

Channel Capacity for Time-Resolved Effective Connectivity in Functional Neuroimaging

Understanding how brain regions influence one another over time is a central goal of neuroscience. However, existing approaches to effective connectivity often involve tradeoffs among mechanistic interpretability, computational scalability, and time-resolved estimation. Here, we introduce information channel capacity, a model-based measure of directed information transfer between brain regions, and combine it with a sliding-window framework to estimate time-varying directional interactions. We validate channel capacity across multimodal neuroimaging datasets in humans and rodents because this breadth is needed to test three complementary properties that no single dataset can establish alone: sensitivity to evoked information transfer, specificity against false-positive directional effects, and the ability to capture meaningful temporal variability in directed brain-network interactions. Human motor-task fMRI tests sensitivity, showing that channel capacity detects task-related increases in directed interactions and stronger directional effects during task than during rest in motor-related regions. Concurrent rat local field potential (LFP)-fMRI tests specificity, showing minimal spurious directional asymmetry relative to scan-to-scan variability and consistent temporal dynamics across neural and BOLD signals. Mouse Ca2+-fMRI tests temporal variability, showing that channel-capacity patterns identify reproducible connectivity states and transitions over time. Together, these results establish channel capacity as a physiologically grounded framework for measuring dynamic directional interactions across species and neuroimaging modalities.

neuroscience↗

bioRxiv2026

Paternal behavior is controlled by preoptic Trpc5 neurons

Male parenting behavior is highly conserved and activated only after offspring are born. Here we show that the behavioral switch from infanticide in virgin male mice to caregiving in wild-type sires is associated with enhanced expression and activation of Transient receptor potential channel 5 (Trpc5) in estrogen receptor (Esr1)-expressing neurons in the hypothalamic medial preoptic area (MPOA). While selective deletion of Trpc5 from Esr1MPOA neurons diminishes paternal behavior in sires, overexpression of Trpc5 in these neurons converts the otherwise infanticidal virgin males to exhibit care to pups. Mechanistically, Trpc5-dependent changes in neuronal excitability underlie fatherhood-associated Esr1MPOA neuron plasticity. Notably, Trpc5 overexpression also enhances escape behavior and elicits exploratory diving behavior, suggesting that these neurons control a broader adaptive parenting response in males. These findings establish a Trpc5-dependent MPOA neural signal as a critical regulator of paternal behavior.

neuroscience↗

bioRxiv2026

THIK-1 channel mediates microglial glucose sensing and modulates AgRP neurons

Microglia play essential roles in maintaining energy homeostasis, and their dysfunction contributes to metabolic disease. Although high-fat diet (HFD) exposure induces microglial activation, the underlying mechanisms remain poorly defined. Here, we identified a previously unrecognized role for THIK-1 channel in mediating glucose sensing of microglia in arcuate nucleus of the hypothalamus (ARH), during HFD-induced obesity. Pharmacological inhibition of THIK-1 channel with tetrapentylammonium (TPA) suppresses feeding and attenuates body-weight gain in diet induced obese mice. Mechanistically, inhibition of agouti-related peptide (AgRP) neurons is indispensable for TPA-induced hypophagia. Moreover, THIK-1 inhibition promotes microglial phagocytosis of perineuronal nets (PNNs), leading to reduced AgRP neuronal activity and feeding suppression. Together, these findings establish THIK-1 as a critical glucose sensor in hypothalamic microglia and uncover a microglia-dependent pathway through which overnutrition modulates AgRP neuronal activity via PNN remodeling to regulate energy balance, highlighting THIK-1 as a potential therapeutic target for treatment of diet-induced obesity.

neuroscience↗

bioRxiv2025

Deep Learning for Cognitive Task Presence Prediction from Dynamic Functional Connectivity

Dynamic functional connectivity (dFC) studies the time-varying coordination between brain regions measured with fMRI and is a potential biomarker for understanding cognitive dynamics and tracking the development of neurological disorders. However, a critical methodological challenge lies in the variability of dFC estimates across different dFC assessment methods, raising concerns about the reliability and interpretation of downstream findings. While deep learning (DL) models have demonstrated the ability to capture traditionally inaccessible data patterns in many disciplines, they encounter challenges when applied to neuroimaging data. For instance, the high dimensionality, noise, and temporal complexity inherent in dFC makes it challenging for DL models to extract meaningful and interpretable insights. In this study, we investigated how DL architectures can be developed and adapted to predict task presence over time from task-based dFC data, and additionally, how the choice of dFC assessment method influences the predictive performance of DL models. We developed and compared a convolutional neural network (CNN), a node-level classification graph convolutional network (GCN), and a graph-level classification GCN based on their ability to predict time points at which subjects were performing a cognitive task or at rest. In our study, the results indicate that both DL model architecture and dFC estimation methodology significantly impact task presence prediction capacity, while the specific task paradigm had minimal influence out of the limited types that were explored. This work offers a powerful benchmark for understanding the dynamics of underlying task-driven cognitive state transitions and the analytical flexibility limitations of dFC estimation methods and DL architectures.

neuroscience↗

bioRxiv2025

Integrated multi-omic and functional evidence uncover substantial strain-specific divergence in zebrafish

The zebrafish (Danio rerio) is a foundational vertebrate model in biomedical and developmental research, yet genetic divergence among laboratory strains remains an underappreciated source of biological and experimental variation. Among these, the AB and Tubingen (TU) strains are used globally, forming the basis for most zebrafish-based discoveries. Here, we integrated long- and short-read sequencing, ATAC-seq, Hi-C, transcriptomics, and functional assays to generate a comprehensive multi-omic comparison of these two strains. Our analyses revealed substantial genomic and regulatory divergence, including a 62-bp insertion in the asmt promoter that elevates transcription and alters melatonin biosynthesis, driving strain-specific circadian phenotypes. We also identify a non-synonymous variant (mybbp1aG2612C) associated with heightened immune responsiveness. Together, these findings construct the first genome-wide atlas of functional variation between zebrafish strains, illuminating how hidden genetic differences can shape phenotype, regulatory architecture, and experimental reproducibility in this essential vertebrate model.

genomics↗

bioRxiv2024

Kinship analysis and pedigree reconstruction by RAD sequencing in cattle

Kinship and pedigree information, used for estimating inbreeding, heritability, selection, and gene flow, is useful for breeding and animal conservation. However, as the size of the crossbred population increases, inaccurate generation and parentage recoding in livestock farms increases. Restriction-site-associated DNA sequencing (RAD-Seq) is a cost-effective platform for single nucleotide polymorphism (SNP) discovery and genotyping. Here, we performed a kinship analysis and pedigree reconstruction for Angus and Xiangxi yellow cattle, which benefit from good meat quality and yields, providing a basis for livestock management. A total of 975 cattle, including 923 offspring with 24 known sires and 28 known dams, were sampled and subjected to SNP discovery and genotyping. The identified SNPs panel included 7305 SNPs capturing the maximum difference between paternal and maternal genome information allowing us to distinguish between the F1 and F2 generation with 90% accuracy. In addition, parentage assignment software based on different strategies verified that the cross-assignments. In conclusion, we provided a low-cost and efficient SNP panel for kinship analyses and the improvement of local genetic resources, which are valuable for breed improvement, local resource utilization, and conservation.

genomics↗

bioRxiv2023

Whole genome sequencing reveals autooctoploidy in the Chinese sturgeon and its evolutionary trajectories

The Order Acipenseriformes, which include sturgeons and paddlefishes, represent "living fossils" with complex genomes that are good models for understanding whole genome duplication (WGD) and ploidy evolution in fishes. Here we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8 n), a hexavalent (6 n), two tetravalents (4 n), and a divalent (2 n). We propose based on an analysis taking into account delayed rediploidization that its octoploid genome composition results from two rounds of homologous whole genome duplications (WGDs), and further provide insight into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy composition and evolutionary trajectories of polyploidy fishes.

genomics↗

bioRxiv2018

Evaluation of the GenoType MTBDRplus and MTBDRsl for the detection of drug-resistant Mycobacterium tuberculosis on isolates from Beijing,China

The incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR) and extreme drug resistance (XDR-TB) continue to increase alarmingly worldwide and reliable and fast diagnosis of MDR-TB and XDR-TB is essential for the adequate treatment of patients. So molecular line probe assays (LPAs) for detection of MDR-TB and XDR-TB have been endorsed by the World Health Organization (WHO). We analyzed 96 isolates from Beijing comparing culture-based drug susceptibility testing (DST) to LPAs detecting rifampicin (RFP), isoniazid (INH), and levofloxacin (LFX), amikacin (AM), capreomycin (CMP), ethambutol (EMB) resistance. Compared to phenotypic DST, the GenoType MTBDRplus and MTBDRsl showed a sensitivity of 98.7% and a specificity of 88.9% for detection of RFP resistance, 82.1% and 94.4% for INH, 89.7% and 94.4% for LFX, 60.0% and 98.7% for AM/CPM, 57.5% and 98.2% for EMB, respectively. The sensitivity and specificity of LPAs for MDR-TB and XDR-TB were 80.8%, 100% and 50.0%, 97.6%. Mutations in codon S531L of the rpoB gene and S315T1 of KatG gene were dominated in MDR-TB strains. The most frequently observed mutations were in codon A90V of the gyrA gene, A1401G of the rrs gene and M306V of the embB gene, according to the MTBDRsl results. Our study showed that, in combination to phenotypic DST, application of the LPAs might be an efficient and reliable supplementary DST assay for rapid susceptibility screening of MDR-TB and XDR-TB. Using LPAs in high MDR/XDR burden countries allows for appropriate and timely treatment, which will reduce transmission rates, morbidity and improve treatment outcomes in patients.

microbiology↗

bioRxiv2017

Characterization of a Novel Model of Overuse-Induced Calcific Achilles Tendinopathy in Mice: Contralateral Tendinopathy Following Unilateral Tenotomy

ObjectiveTo develop a simple but reproducible overuse induced animal model of Achilles tendinopathy in mice for better understanding the underlying mechanism and prevention of calcific Achilles tendinopathy.\n\nMethods80 C57/B6 mice (8-9 weeks old) were employed and randomly divided into control group and experimental group. Unilateral Achilles tenotomy was performed on the right hindlimb of experiment group. After 12 weeks, the onset of Achilles tedinopathy in the contralateral Achilles tendon was determined by radiological assessment, histological analysis, electron microscopy observation and biomechanical test.\n\nResultsThe onset of calcific Achilles tendinopathy in contralateral Achilles tendon was confirmed after 12 weeks unilateral tenotomy. The contralateral Achilles tendon of experimental group was characterized as hypercelluarity, neovascularization and fused collagen fiber disarrangement, compared to the control group. Importantly, intratendon endochondral ossification and calcaneus deformity was featured in contralateral Achilles tendon. Additionally, poor biomechanical properties in the contralateral Achilles tendon revealed the incidence of Achilles tedinopathy.\n\nConclusionWe hereby introduce a novel simple but reproducible spontaneous contralateral calcific Achilles tendinopathy model in mice, which represents the overuse conditions during the tendinopathy development in human-beings. It should be a useful tool to further study the underlying pathogenesis of calcific Achilles tendinopathy.

animal behavior and cognition↗