Biology subjects

Ming, X.

Publications and source records attributed to Ming, X..

5 recordsLinked to original sources

bioRxiv2026

Listeriolysin O recruits UBA1 to ubiquitinate NLRP3 and suppress inflammasome defence

The NLRP3 inflammasome is a central cytosolic defence pathway against infection, yet intracellular pathogens must restrain this response to preserve their replicative niche. Here we identify a ubiquitin-dependent immune-evasion mechanism in which L. monocytogenes uses listeriolysin O (LLO) to destabilise NLRP3. The N-terminal PEST-like sequence of LLO acted as an adaptor that recruited the host ubiquitin-activating enzyme UBA1 and promoted K48-linked polyubiquitination of NLRP3. This modification drove proteasomal NLRP3 degradation and limited caspase-1 activation, gasdermin D cleavage, IL-1{beta}/IL-18 release, and macrophage pyroptosis. Deleting the PEST region preserved basal haemolytic activity but impaired NLRP3 ubiquitination, thereby enhancing inflammasome activation during infection in macrophages and in vivo. Conversely, UBA1 overexpression suppressed NLRP3-mediated inflammatory responses and supported intracellular bacterial survival. UBA1 depletion restored NLRP3 protein levels, reduced bacterial burden and delayed lethal infection, albeit with increased inflammatory tissue injury. These findings define a ubiquitin-hijacking strategy that operates at the E1 step, whereby a bacterial toxin redirects host ubiquitin activation towards an innate immune sensor.

microbiology↗

bioRxiv2025

Harmonizing single cell 3D genome data with STARK and scNucleome

Single-cell three-dimensional genome sequencing (sc3DG-seq) is advancing our understanding of genome regulation and cellular heterogeneity in diverse biological processes. Despite significant technological advancements, a universal tool capable of processing sc3DG-seq data and benchmarking the performance of various techniques in resolving 3D chromatin structures is absent. To fill this gap, we present STARK, a versatile toolkit designed for the preprocessing, quality control and analysis of all spectrum of sc3DG-seq data. Utilizing STARK, we systematically processed 11 sc3DG-seq technologies data, enabling a quantitative benchmarking of each technologys strengths and limitations. Additionally, we developed the EmptyCells algorithm to distinguish high quality from empty barcodes, and introduced the Spatial Structure Capture Efficiency (SSCE) metric to assess the ability of single cells to capture chromatin structures. Furthermore, we established scNucleome, an extensive repository of uniformly processed sc3DG-seq datasets, offering a foundational resource to catalyze further exploration and discovery in the 3D genome research.

bioinformatics↗

bioRxiv2025

FX-Cell: a method for single-cell RNA sequencing on difficult-to-digest and cryopreserved plant samples

Single-cell RNA sequencing (scRNA-seq) in plants requires the isolation of high-quality protoplasts-- cells devoid of cell walls. However, many plant tissues and organs are resistant to enzymatic digestion, posing a significant barrier to advancing single-cell multi-omics research in plants. Furthermore, for many field-grown crops, the lack of immediate laboratory access presents another major challenge for protoplast preparation. To address these limitations, we developed the FX-Cell method and its derivatives, FXcryo-Cell and cryoFX-Cell, to enable scRNA-seq with both difficult-to-digest and cryopreserved plant samples. By optimizing the fixation buffer and minimizing RNA degradation, our approach ensures efficient cell wall digestion at high temperatures while maintaining high-quality single cells, even after long-term storage at -80{degrees}C, and circumvents use of nuclei, which are not representative of the pool of translatable mRNAs. Using these methods, we successfully constructed high-quality cell atlases for rice tiller nodes, rhizomes of wild rice, and maize crown roots grown in field conditions. Moreover, these methods enable the accurate reconstruction of plant acute wounding responses at single-cell resolution. Collectively, these advancements expand the applicability of plant single-cell genomics across a wider range of species and tissues, paving the way for comprehensive Plant Cell Atlases for plant species.

plant biology↗

bioRxiv2023

Hypoxia-induced circSTT3A maintains Breast Cancer Stem Cell formation by Stabilizing PGK1 protein

BackgroundHypoxia is a key feature of tumor microenvironment that can cause fundamental changes in cancer cells, and may also lead to the development of breast cancer stem cells (BCSCs) with self-renewal ability. However, the mechanism of hypoxia in inducing BCSCs is not fully understood. MethodsPerforming RNA sequence and bioinformatics analysis, a hypoxia specific circular RNA (circRNA), named circSTT3A, was identified in hypoxic breast cancer cells and tissues. The clinical significance of circSTT3A was investigated in breast cancer (BC) tissues and tissue array. The loss and acquisition of circSTT3A were carried out in vivo and in vitro to confirm its functional roles in BCSC stemness maintenance. HIF1 droved circSTT3A expression was evaluated by chromatin immunoprecipitation and dual luciferase reporter assays. RNA pull-down, RNA immunoprecipitation, silver staining detection, mass spectrographic analysis, co-immunoprecipitation assays and western blotting were exerted to determine circSTT3A directly binding with HSP70 and PGK1 proteins. CircSTT3A-mediated serine metabolism was determined by UHPLC-QTRAP-MS system and ELISA kit. BC mouse model was used to assess the effects of circSTT3A/Hsp70/PGK1 on tumorigenesis and chemotherapy resistance in vivo. ResultsA novel hypoxia specific circSTT3A was significantly upregulated in clinical breast cancer tissues, and was related to the clinical stage and poor prognosis of BC patients. The hypoxia inducible factor 1 alpha (HIF1)-regulated circSTT3A has remarkable effect on mammosphere formation in breast cancer cells. Our work revealed that circSTT3A directly interacting with nucleotide-binding domain of heat shock protein 70 (HSP70) increases the ability of HSP70 to recruit phosphoglycerate kinase 1 (PGK1) via its substrate-binding domain, which reduces the ubiquitination of PGK1 and increases the stability of PGK1. The enhanced PGK1 catalyzes 1,3-diphosphoglycerate (1, 3-BPG) into 3-phosphoglycerate (3-PG) leading to 3-PG accumulation and increase of serine synthesis, thus to facilitate BCSC enrichment under hypoxic microenvironment. Loss of circSTT3A or PGK1 substantially induces suppression in tumor initiation and tumor growth, which dramatically increases tumor sensitivity to Doxorubicin treatment in mice. ConclusionsHypoxia induced circSTT3A/HSP70/PGK1 axis plays a critical role in maintaining BCSC properties and may be meaningful for treating patients with breast cancer.

cancer biology↗

bioRxiv2022

Responses of Agricultural plants to Lithium pollution: Trends, Meta-Analysis, and Perspectives

Lithium (Li) is gaining attention due to rapid rise of modern industries but their ultimate fingerprints on plants are not well established. Herein, we executed a meta-analysis of the existing recent literature investigating the impact of Li sources and levels on plant species under different growth conditions to understand the existing state of knowledge. Toxic effects of Li exposure in plants varies as a function of medium and interestingly, more negative responses are reported in hydroponic media as compared to soil and foliar application. Additionally, toxic effects of Li vary with Li source materials and LiCl more negatively affected plant development parameters such as plant germination (n=48) and root biomass (n=57) and recorded highly uptake in plants (n=78), while LiNO3 has more negative effects on shoot biomass. The Li at <50 mg L-1 concentrations significantly influenced the plant physiological indicators including plant germination and root biomass, while 50-500 mg L-1 Li concentration influence the biochemical parameters. The uptake potential of Li is dose dependent and their translocation/bioaccumulation remains unknown. Future work should include complete lifespan studies of the crop to elucidate the bioaccumulation of Li in edible tissues and to investigate possible trophic transfer of Li. Environmental significanceAccumulation of Li sources is increasing in ecosystem compartments, and this might be vulnerable to plants.

plant biology↗