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Xu, X.

Publications and source records attributed to Xu, X..

At least 109 records · Page 6Linked to original sources

Chromosome-level genome assembly of Helichrysum odoratissimum, a medicinal plant from Southern Africa

Helichrysum odoratissimum, a plant species native to Southern Africa, holds deep cultural significance and is widely used in traditional medicine. It is valued for its antimicrobial and anti-inflammatory properties and is cultivated and traded in South Africa due to its growing commercial relevance to the pharmaceutical and cosmetic industries. Despite its ecological and economic importance, genomic resources for this species remain limited. Here, we report a high-quality chromosome-level genome assembly for H. odoratissimum to facilitate investigations into its genetic basis of bioactivity, environmental adaptation, and taxonomic relationships. High-molecular-weight DNA extracted from leaf tissue was sequenced using Oxford Nanopore Technologies (ONT) long-read sequencing, and Hi-C proximity ligation data were generated to enable chromosome-scale scaffolding. The final assembly spans 2.4 Gb, with a scaffold N50 of 354 Mb, and was anchored and oriented into seven chromosomes, with 2,935 smaller scaffolds remaining unplaced. Assembly quality and completeness were evaluated using QUAST and BUSCO, and chromosomal structure was validated using Hi-C contact maps. This genome provides a foundational resource for functional genomics, conservation planning, molecular breeding, and the discovery of bioactive compounds underpinning the medicinal and commercial value of H. odoratissimum.

genomics↗

Cell Type Architecture and Positional Gene Gradients in an Adult Animal at Subcellular Resolution

The spatial organization of cell types and gene expression underlies tissue architecture and organismal physiology. However, resolving complete cellular and molecular landscapes within a three-dimensional context remains challenging, particularly in organisms with high cellular heterogeneity and complex geometry. Here, we developed a semi-supervised workflow to reconstruct high-resolution three-dimensional spatial transcriptomic models of the planarian Schmidtea mediterranea at single-cell resolution. Planarians are basal bilaterians capable of regenerating body structures after injury. Our reconstruction maps the distribution of cell types and spatially patterned gene expression across the intact organism and identifies 119 candidate positional control genes (PCGs). These genes are expressed across muscle, neural, and epidermal populations. Functional perturbation of selected candidates, including pitx3, ptpn11, pi4ka, upf3b, and cul1, revealed roles in regeneration following injury. In addition, we identify intestinal cells as prominent components of the microenvironment surrounding adult tgs1 pluripotent stem cells (neoblasts). Together, these results demonstrate the utility of three-dimensional spatial transcriptomic reconstruction for mapping cellular architecture and positional gene regulation in complex adult organisms.

developmental biology↗

4D Single-Cell Spatial Transcriptomics Reveals Dynamic Morphogenetic Gradients and Regenerative Domains in Planarians

Regeneration relies on precise spatiotemporal gene expression and cellular responses to establish tissue identity and body patterning. Using high-resolution Stereo-seq (715 nm) on 353 sections from 16 whole animals at 8 regeneration timepoints, we constructed a 4D spatiotemporal transcriptomic map of planarian regeneration. Our analysis captured 36 refined cell types from 3,508,004 segmented cells, enabling genome-wide transcriptional imputation of gene expression dynamics across body axes at cellular, tissue, and organismal scales. We identified dynamic positional gradients and distinct spatially distributed cell types during regeneration, including an injury-induced Anterior Regenerative Zone (ARZ). The ARZ exhibited enriched positional signals in epidermal, muscle, and neural cells and was regulated by Mediator 8, which is crucial for polarity remodeling and blastema formation. This study provides a comprehensive spatial molecular and cellular map of regenerative processes, highlighting injury-induced spatial domains and key regulatory factors in planarian regeneration. We also provide an interactive web portal, offering a valuable resource for exploring and analyzing regeneration mechanisms in a spatiotemporal context.

developmental biology↗

ATLAS: Population-Level Disease Locus Discovery via Differential Attention in Genomic Language Models

Identifying disease-associated genetic variants remains a key challenge in genomics, especially in small cohorts or for rare and complex mutation types where genome-wide association studies (GWAS) often fall short. We introduce ATLAS, a population-level framework that leverages attention signals from pretrained genomic language models (gLMs) to detect disease-associated genes and loci directly from raw sequences--without requiring explicit variant calls or supervised training. ATLAS first performs gene-level differential attention analysis to prioritize candidate genes, followed by base-level analysis to localize disease-associated regions at single-haplotype resolution. We validate ATLAS on synthetic and {beta}-thalassemia datasets, demonstrating robust performance across diverse allele frequencies (down to 10%), cohort sizes (below 200 individuals per group), and genomic scales. Compared to GWAS, ATLAS achieves higher recall of known loci and captures haplotype-specific signals missed by traditional methods. Cross-model benchmarking further shows that precise localization depends on both model size and pretraining on diverse human genomes. In summary, ATLAS offers a scalable, sequence-native alternative to traditional statistical genetics.

genetics↗

Promoter editing of starch branching enzyme IIb and granule-bound starch synthase I balances resistant starch content and amylose content in rice

Increasing attention is being focused on the glycemic index (GI) of daily food for humans, and the resistant starch content (RSC) is an important indicator of GI for starch-rich staple foods. In recent years, some studies revealed that the loss function of single or multiple key enzymes in the primary pathway of starch synthesis substantially increases RSC in rice, such as starch branching enzyme IIb (BEIIb) and soluble starch synthase IIIa (OsSSIIIa). However, a noteworthy negative characteristic of these high RSC mutants is the substantially increased amylose content (AC). AC as a major determinator of rice eating quality, must not be higher than an acceptable limit for most consumers. To solve this problem, in this study, we adopted two promoter editing (PE) editing strategies to develop rice germplasms with a better balance of RSC and AC: one is to edit the promoter of BEIIb in a low AC rice variety, another is to edit the promoter of Waxy (Wx) gene in a BEIIb loss of function mutant. Using AC[≤]20%, which is the range of premium quality rice in China as a criteria, we finally obtained 2 homozygous lines with significantly increased RSC ([≥]5%) in the NG46 background by promoter editing of BEIIb and 1 homozygous line in the YouTang2 (YT2, a BEIIb mutant) background by promoter editing of Wx gene. Further analysis revealed that AC and the amount of long-chain branches of amylopectin are positively correlated with RSC in the population of BEIIb PE lines. However, unexpectedly, the Wx PE-line with substantially decreased AC (17.7%) also showed significantly increased RSC (16.9%). Our study not only produces useful germplasms for the high RSC rice breeding in the future but also provides an insight into understanding the relationship between AC and RSC in defective BEIIb rice.

plant biology↗

Computational modeling of head direction cells in three-dimensional space: directional encoding and visual cue manipulation

Head direction (HD) cells can fire selectively as a function of the animals head azimuth direction and form an internal compass for navigation. They were found in the mammalian limbic system including the dorsal presubiculum and entorhinal cortex. The underlying network updates its directional estimate in a self-organized fashion and can be recalibrated by external sensory cues. Although ring-attractor models were proposed to account for azimuth coding on horizontal planes, they cannot explain conjunctive azimuth-and-pitch tuning observed in HD cells of the presubiculum of flying bats navigating in three-dimensional (3-D) space. Based on the 3-D electrophysiological recordings, we developed a toroidal continuous attractor network that jointly encodes horizontal azimuth and vertical pitch angle of head direction. The model can reproduce the experimentally recorded tuning curves of individual HD cells, and accurately encode the 3-D dynamic head direction of bat by HD cell population. The model also simulate the influence of horizontal visual cue manipulation on the HD system in 3-D space and predicts how horizontal landmark rotation induces a sustained azimuthal offset that persists after the cue is removed, which is comparable to two-dimensional experimental findings. This research clarifies how conjunctive 3-D direction codes are generated and modified by vestibular input, visual information and recurrent connectivity. It also uncovers the computational principles and properties of the brains navigation functions in realistic 3-D environments and offers new theoretical reference for future studies. Author summaryA central function of the brains navigation system is to track head direction, which in terrestrial mammals is largely confined to a horizontal plane. However, for animals like bats that navigate freely in three-dimensional (3-D) space, the neural code for head direction has been found to be high-dimensional. While ring attractor network models elegantly explain horizontal azimuth coding, how the 3-D head direction code is formed and affected by sensory information remains unknown. Here, we develop a toroidal continuous attractor network model with vestibular and visual modules that explains the jointly encoding of azimuth and pitch angles, and the effect of visual cue. We introduce the toroidal topology to the continuous attractor network, and the high-dimensional angular velocity signal from vestibular system and visual input are used to update the population dynamics of the network. Our model is constrained by and reproduces 3-D electrophysiological data from flying bats, captures the unique tuning curves of individual head direction cells, and further achieves the accurate encoding of dynamic 3-D head movements by population activity. Evidences in the rodent have suggested visual cue manipulation recalibrates head direction coding horizontally. Our model further successfully simulates the influence of visual cue rotation in 3-D space, predicting a persistent, global offset in the azimuth encoding--an effect that endures after cue removal and aligns with 2-D rodent experimental phenomena. This work provides a mechanistic, network-level explanation for 3-D head direction encoding and reveals how multimodal cues are integrated to form the internal compass in a volumetric world.

neuroscience↗

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

An Integrated Single-Cell and Epigenomic Resource for Comparative Analysis of the Basal Ganglia

The basal ganglia regulate motor, cognitive, and affective behaviors, and their dysfunction underlies diverse neurological and psychiatric disorders. Comprehensive, accessible multi-omics resources are needed to understand the regulatory mechanisms governing basal ganglia cell types. Here we present an open, interactive web-based platform for exploring single-cell multi-omics datasets from basal ganglia, generated using 10X Multiome, snm3C-seq, and Paired-Tag technologies from the BICAN (NIH BRAIN Initiative Cell Atlas Network) consortium. The platform is available at https://basalganglia.epigenomes.net/ and enables integrated visualization of gene expression, chromatin accessibility, DNA methylation, histone modifications, and chromatin conformation across cell types and human, macaque, marmoset, and mouse species, with direct genome browser support and comparative epigenomic functionality. Representative analyses demonstrate cell-type-specific regulatory landscapes, conserved and species-specific regulatory elements, and links between epigenomic regulation and transcription. This resource provides a scalable, community-oriented foundation for advancing basal ganglia biology and interpreting regulatory mechanisms relevant to brain function and disease. HighlightsO_LIIntegrated single-cell epigenomic resource for basal ganglia C_LIO_LIInteractive genome browser enables multi-omics and cross-species exploration C_LIO_LIReveals cell-type-specific and species-specific regulatory landscapes C_LIO_LISupports community access to complex brain epigenomic datasets C_LI

genomics↗

A curvilinear coordinate flatmap for visualizing hippocampal structure and development

The hippocampal formation is a highly curved and topographically complex forebrain structure. This complex geometry presents persistent challenges for analyzing subregional, laminar, and connectivity patterns. Here, we present a computational workflow that generates curvilinear-coordinate flatmaps from Common Coordinate Framework (CCF) registered hippocampal and retrohippocampal regions by solving the Laplacian equation to derive geodesic streamlines. This transformation unfolds the hippocampus into a planar slab, bounded by the meningeal and ventricular surfaces, with the depth defined along the radial axis. We apply this transform to image volumes, single neuron reconstructions, and point data, including spatial transcriptomic and rabies tracing datasets, revealing topographic variations in the dorsoventral and radial axes that are obscured in the CCF coordinate space. As proof of principle, we use flatmaps to show connectivity loss in a mouse model of Alzheimers disease and track postnatal development of microglial distribution in the hippocampus. This work provides an efficient and accessible resource for visualizing hippocampal organization across development and disease, offering new opportunities to interrogate the structure and function of this important brain region.

neuroscience↗

Chromosome-level genome assembly and annotation of the degu (Octodon degus)

High-quality reference genomes are essential for comparative and functional genomics yet remain unavailable for many emerging model organisms. Here, we report OctDeg2.0, a chromosome-level genome assembly and annotation of the degu (Octodon degus), generated using PacBio HiFi long-read sequencing and Hi-C scaffolding from a single male individual. Octodon degus is of growing interest as a natural animal model for aging and Alzheimers disease research. The 3.4 billion base-pair assembly comprises 28 autosomes and both sex chromosomes, with markedly improved contiguity and completeness over the prior short-read assembly while maintaining high base accuracy. The new assembly provides substantially enhanced gene annotation, clearer resolution of chromatin architecture and cis-regulatory element landscapes, with much improved characterization of repetitive and structurally complex regions, including centromeres and segmental duplications. We present a streamlined and reproducible pipeline for high-resolution de novo genome assembly and gene annotation applicable to other emerging model organisms. This work establishes a robust genomic resource for studying molecular and cellular mechanisms in health and disease in Octodon degus.

genomics↗

Molecular and Cellular Underpinnings of Spatial Heterogeneity in Fetal Cortical Folding

Cortical folding is a defining feature of human brain development, yet the molecular and cellular mechanisms that produce regionally specific cortical folding remain incompletely understood. Here we combined high-resolution in-utero T2-weighted and diffusion MRI atlases (23-38 weeks of gestational age) with prenatal transcriptomic profiles to map regional macrostructural and microstructural features of cortical folding to underlying gene expression. We found genes whose expression patterns correlated with cortical curvature were enriched for neurogenesis, progenitor proliferation and radial glia guided neuronal migration, and localized to ventricular zone/subventricular zone progenitor cell subtypes, supporting for the protomap hypothesis of areal specification. By contrast, cortical microstructural markers-associated gene sets were implicated in myelination, cell adhesion and extracellular matrix remodeling, and mapped to astrocyte and endothelial cell programs. The microstructure-related gene expression peaked in the early postnatal period and remained high throughout childhood, while the curvature-associated gene expression reduced with age. Several of these cortical folding-related genes overlapped with autism spectrum disorder risk loci (e.g., SCN2A, STXBP1, DVL3). Collectively, these cross-modal findings outline a sequential developmental architecture--early progenitor driven patterning followed by myelin and extracellular matrix consolidation. In addition, we released a high-resolution fetal labeling atlas to facilitate further imaging-genetic studies of early cortical development.

neuroscience↗

Antitoxin-induced auto-phosphorylation neutralizes the nucleotidyltransferase toxin AbiEii from Streptococcus agalactiae to safeguard global translation

Nucleotidyltransferases (NTases) control diverse physiological processes, including DNA replication and repair, antibiotic resistance, and RNA modification. The Streptococcus agalactiae abortive infection family toxin, AbiEii, belongs to the DUF1814 superfamily of NTases and blocks bacterial growth through an as yet unknown mechanism. Antitoxin AbiEi has been reported to antagonize AbiEii as part of a Type IV toxin-antitoxin system. Here, we demonstrate through structural, biochemical, and biophysical studies that AbiEi binds to AbiEii to form a stable toxin-antitoxin complex in solution. Antitoxin binding ultimately leads to AbiEii auto-phosphorylation and an abolition of NTase activity. These data reclassify AbiE systems as Type VII toxin-antitoxin systems. Toxin phosphorylation appears to be a dynamic and reversible process, and we show that the sole serine/threonine phosphatase SaSTP of S. agalactiae can efficiently dephosphorylate AbiEii in vitro. Mutagenesis studies and functional assays indicate that a widespread mechanism of toxin auto-phosphorylation accounts for AbiEii neutralization, further supporting recent hypotheses outlining control of homologous MenAT toxin-antitoxin systems from Mycobacterium tuberculosis.

molecular biology↗

Preparation and application of YFV-17D-derived Anterograde Trans-neuronal Viral Vectors for Neuroscience Research

Trans-neuronal viruses that spread between synaptically connected neurons have become invaluable tools in neuroscience, enabling circuit mapping and targeted delivery of genetic material to cells within defined pathways. Although most available trans-neuronal viral tracers propagate retrogradely, an anterograde trans-neuronal virus that spread from presynaptic to postsynaptic neurons would substantially expand experimental capabilities. We previously demonstrated that YFV-17D--a live attenuated yellow fever vaccine used clinically for decades--spreads anterogradely along neuronal circuits. We further developed a suite of recombinant YFV-17D-based vectors for diverse applications, including tracing monosynaptic projectome of defined neuronal cell types, multiplex mapping of parallel pathways, and trans-neuronal genetic manipulation with minimal neurotoxicity. We have now tested and optimized procedures for vector production and application. Based on these optimizations, here, we present a two-part guide for preparing and deploying this viral vector system to map brain connectivity. The first part describes the molecular biology and cell culture workflows required to generate high-quality viral vectors, yielding titers of [~]1 x 10^10 to 5 x 10^11 genomic copies per milliliter within approximately two weeks. The second part outlines optimized animal procedures, including intracranial injections, perioperative care, and experimental considerations tailored to specific aims and vector variants. Depending on the application, efficient trans-neuronal tracing can be achieved within 1-4 weeks following delivery.

neuroscience↗

A Unified and Interpretable Framework for Evaluating Fluorescence Trace Quality in Transcription Kinetics

Quantifying transcriptional dynamics from fluorescence traces is a powerful approach to understanding gene regulation, but such analysis critically depends on the quality of the fluorescence signal. Experimental researchers often lack an objective and computationally simple way to assess trace quality before kinetic modeling. In this study, we fill in this gap via systematically investigating two key factors (i.e., signal-to-noise ratio (SNR) and trace length) using synthetic data generated from a composite-state Hidden Markov Model (cpHMM) simulator. By analyzing thousands of simulated traces, we identified quantitative thresholds (SNR [≥] 30 dB and length [≥] 360) beyond which transcriptional dynamics can be reliably captured for kinetic inference. Building on these findings, we further discovered a unified and easily computable quality indicator based on the difference between the first two autocorrelation lags. A threshold value of approximately 0.07 effectively separates reliable from low quality traces, providing a simple yet robust criterion for data selection. Together, these results establish a practical framework for assessing fluorescence trace reliability, offering experimental researchers an interpretable and computationally efficient tool to ensure data quality prior to transcription kinetics modeling.

bioinformatics↗

Identification of distinct functions of GLIS3 in β-cell generation critical to prevention of neonatal diabetes

GLIS3 plays a critical role in pancreatic {beta} cells and diabetes, being one of only a few genes implicated in Type 1, Type 2, and Gestational diabetes. In addition to {beta} cells, GLIS3 is expressed embryonically in bipotent and proendocrine progenitor cells, suggesting a role in endocrine lineage development in mice. We hypothesize that GLIS3 is playing important roles in endocrine development as well as during {beta} cell differentiation. We utilized single cell RNA-sequencing at three different timepoints (embryonic day (e)13.5, e15.5, and e18.5) and single nucleus (sn)ATAC-sequencing at e15.5 in both wild type (WT) and Glis3 Knockout (Glis3KO) mouse embryos. This analysis revealed that the numbers of bipotent, proendocrine progenitor, and all subsequent endocrine cells were proportionately reduced in Glis3KO mice. Additionally, loss of GLIS3 function generates a unique subpopulation of cells that fail to upregulate Ins2 transcription and downregulate expression of several ribosomal and oxidative phosphorylation genes normally repressed during pre{beta} to {beta} cell differentiation. Our study therefore shows that GLIS3 regulates two distinct stages: the embryonic generation/differentiation of bipotent cells and the differentiation of pre{beta} to {beta} cells. Dysregulation of these two stages provides a causal mechanism for the development of neonatal diabetes in GLIS3-deficiency.

developmental biology↗

Coronavirus Nucleocapsid Proteins Hijack Host Protein Kinase A Catalytic Subunit α into Nucleus to Evade from STAT1 Signaling

The role of the cAMP/PKA pathway in antiviral innate immunity, including during coronavirus infections, remains unclear. We discovered coronavirus N proteins initiate cAMP-ADCY10-PKA cascade. Cytoplasmic PKA activates STAT1 independently of canonical JAK/TYR2 signaling. Coronavirus N proteins, via a conserved arginine (e.g., PEDV R58, SARS-CoV-2 R92), directly bind and sequester PKA C into the nucleus to evade STAT1 activation. Using PEDV as a model, mutant viruses with NmutNLS and NR58A were generated. Wildtype PEDV infection suppressed STAT1 activation in cells expressing PKA C/PKA CS339A deficient in STAT1 phosphorylation. However, in rXS0101mutNLS- or rXS0101R58A-infected cells, only PKA CS339A expression inhibited STAT1 activation. Downregulation of STAT1 activation is accompanied with increased viral replication. This study first elaborates that PKA C activates STAT1 in the cytoplasm of infected cells distinctly from canonical JAK/STAT1 signaling, while coronaviruses evade this antiviral response by sequestering PKA C into the nucleus via direct N protein interaction.

microbiology↗

OmniCell: Unified Foundation Modeling of Single-Cell and Spatial Transcriptomics for Cellular and Molecular Insights

A cells transcriptional programme is not fully defined by gene expression alone, but by the tissue context in which that programme is enacted. Single-cell RNA sequencing resolves molecular identity after dissociation, whereas spatial transcriptomics preserves tissue architecture but remains constrained by assay-specific sparsity and gene coverage. Here we present OmniCell, a tissue-contextual transcriptomic foundation model pretrained on 67 million dissociated and spatially resolved profiles. By integrating gene identity, expression magnitude and tissue context, OmniCell links transcriptional programmes to the cellular neighbourhoods and anatomical contexts in which they operate. OmniCell organised transcriptomes across molecular, cellular and tissue scales. It recovered cell-type-specific programmes and tissue-aligned gene modules, preserved robust cell-state structure across batches, species and rare populations, and improved the reconstruction of spatial cell identity, anatomical domains and cell-type composition. In human liver cancer Stereo-seq data, OmniCell resolved a tumour-margin transition zone characterised by immune infiltration, acute-phase inflammation, coagulation/complement activity and metallothionein-linked metal-ion detoxification. Contextual gene-embedding similarity analysis showed that gene relationships differed across tumour core, transition-zone and paratumour/adjacent non-malignant niches, indicating that OmniCell captures tissue-dependent gene function rather than expression similarity alone. In mouse brain development and macaque cortex, spatial virtual perturbations mapped regulatory genes onto stage- and region-specific anatomical programmes. Together, these results establish tissue context as a primary axis of transcriptomic representation and provide a framework for studying how cellular programmes acquire context-dependent biological meaning in intact tissues.

bioinformatics↗

UC Irvine Brain Initiative Cell Atlas Network (BICAN) Brain Procurement Program for the Center for Multiomic Human Brain Cell Atlas Project

High-quality neurotypical postmortem human brain tissue is essential but difficult to obtain for constructing comprehensive human brain cell atlases. Here we describe the establishment of UC Irvines Brain Procurement Program, a coordinated initiative to collect and process neurotypical donor brains for multiomic mapping studies within the NIH BRAIN Initiative Cell Atlas Network (BICAN) consortium. Through partnerships with the Orange County Coroners Office, the UC Irvine Willed Body Program, UCI Medical Center, and the Childrens Hospital of Orange County, we have developed standardized workflows encompassing donor identification, postmortem brain recovery and processing, region-of-interest dissection, neurotypical donor selection, and data management. Our experience demonstrates the feasibility of a community-based, multi-institutional procurement framework while highlighting challenges in recruiting neurotypical donors and ensuring demographic representation reflective of Southern California. We further identify opportunities to strengthen outreach and donation pathways. This program provides a scalable model for advancing population-reflective, high-quality human brain cell atlas efforts. HighlightsO_LIEstablish a multi-site pipeline for procuring high-quality neurotypical human brains. C_LIO_LIDemonstrate feasibility of donor collection across childhood to adulthood. C_LIO_LIIdentify barriers and propose strategies to improve broad donor recruitment. C_LI

neuroscience↗