Biology subjects

Gou, M.

Publications and source records attributed to Gou, M..

6 recordsLinked to original sources

bioRxiv2025

CenSegNet: a generalist high-throughput deep learning framework for centrosome phenotyping at spatial and single-cell resolution in heterogeneous tissues

Centrosome abnormalities (CA) are a hallmark of epithelial cancers, yet their spatial complexity and phenotypic heterogeneity remain poorly resolved due to limitations in conventional image analysis. We present CenSegNet (Centrosome Segmentation Network), a modular deep learning framework for high-resolution, context-aware segmentation of centrosomes and epithelial architecture across diverse tissue types. Integrating a dual-branch architecture with uncertainty-guided refinement, CenSegNet achieves state-of-the-art performance and generalisability across both immunofluorescence and immunohistochemistry modalities, outperforming existing models in accuracy and morphological fidelity. Applied to tissue microarrays (TMAs) containing 911 breast cancer sample cores from 127 patients, CenSegNet enables the first large-scale, spatially resolved quantification of numerical and structural CA at single-cell resolution. These CA subtypes are mechanistically uncoupled, exhibiting distinct spatial distributions, age-dependent dynamics, and associations with histological tumour grade, hormone receptor status, genomic alterations, and nodal involvement. Structural CA levels are additionally associated with overall survival, supporting the clinical relevance of spatially resolved CA patterns. Discordant CA profiles at tumour margins are linked to local aggressiveness and stromal remodelling. To support broad adoption and reproducibility, CenSegNet is released as an open-source Python library. Together, our findings establish CenSegNet as a scalable, generalisable platform for spatially resolved centrosome phenotyping in intact tissues, enabling systematic dissection of the biology of this organelle and its dysregulation in cancer and other epithelial diseases.

cell biology↗

bioRxiv2024

Phages-bacteria interactions underlying the dynamics of polyhydroxyalkanoates-producing mixed microbial cultures via meta-omics study

The dynamics of the structure of polyhydroxyalkanoates-producing mixed microbial cultures (PHA-MMCs) during enrichment and maintenance is an unsolved problem. The effect of phages has been proposed as a cause of dynamic changes in community structure, but evidence is lacking. To address this question, we enriched five PHA-MMCs and sampled temporally to study the interactions between phage and prokaryotic members by combining metagenomics and metatranscriptomics. 963 metagenome-assemble genomes and 4294 phage operational taxonomic units were assembled from bulk metagenomic data. There were complex interactions between the phages in Casadabanvirus and Unclassified Hendrixvirinae and the dominant species in Azomonas, Paracoccus, Thauera and Breundimonas. The dynamic change of the structure of phage and prokaryotic communities were remarkably consistent. Further structural equation modeling analysis showed that phage communities could significantly affect the activity and community structure of prokaryotic microorganisms. In addition, seven key auxiliary metabolic genes (phaC, fadJ, acs, ackA, phbB, acdAB and fadD) in the PHA synthesis pathway were identified from phage sequences. Importantly, these auxiliary metabolic genes were expressed at the transcriptional level, indicating that they were in an active functional state. This meta-analysis provides the first catalog of phages in PHA-MMCs and the auxiliary metabolic genes they carry, as well as how they play a role in the dynamic changes of prokaryotic communities. This study provides a reference for subsequent studies on understanding and regulating the microbial community structure of artificial open microbial systems. ImportanceThe synthesis of biodegradable plastic PHA from organic waste through mixed microbial cultures (MMCs), with extremely low cost, has the potential for expanded production. However, there is a gap of understanding of the dynamics of dominant species in MMCs to better control community structure. Our results demonstrate for the first time the impact of phages on the structure of prokaryotic communities in the MMCs. There are complex interactions between the PHA producers (Azomonas, Paracoccus, Thauera) and phages (Casadabanvirus and Unclassified Hendrixvirinae). Phage communities can negatively regulate the activity and structure of prokaryotic communities. In addition, the auxiliary metabolic genes in the PHA synthesis pathways carried by phages may promote the PHA synthesis ability of prokaryotic members. This study highlights the impact of phages on prokaryotic community structure, suggesting that phages have the potential to become a tool for better controlling the microbial community structure of PHA-MMCs.

microbiology↗

bioRxiv2022

How do Vampires Suck Blood?

Lampreys are blood-sucking vampires in the marine. From a survival perspective, it is expected that lamprey buccal gland exhibits a repository of pharmacologically active components to modulate the hosts homeostasis, inflammatory and immune responses. Several proteins have been found to function as anticoagulants, ion channel blockers, and immune suppressors in lampreys, while small metabolites have never been explored in detail. In this study, by analyzing the metabolic profiles of 14 different lamprey tissues, we have identified two groups of blood-sucking-associated metabolites, i.e., kynurenine pathway metabolites and prostaglandins, in the buccal gland and they can be injected into the host fish to ensure a steady and sustained blood flow to the feeding site. These findings demonstrate the complex nature of lamprey buccal gland and highlight the diversity in the mechanisms utilized for blood-sucking in lampreys. In addition, a lamprey spatial metabolomics database (https://www.lampreydb.com) was constructed to assist studies using lampreys as model animal. The database contains detailed qualitative, quantitative, and spatial distribution information of each detected metabolite, and users can easily query and check their metabolites of interest, and/or identify unknown peaks using the database. Significance StatementLampreys are one of the two surviving jawless vertebrate groups that hold the key to our understanding of the early vertebrate evolution, adaptive immune origin, and developmental neurobiology. Here, we applied a spatial metabolomics approach to study the lamprey-host interaction. Two groups of metabolites, i.e., kynurenine pathway metabolites and prostaglandins, were found in the lamprey buccal gland, which modulate the hosts homeostasis, inflammatory and immune responses. The establishment of the first tissue-wide spatial lamprey metabolomics database in this study facilitate future studies in biochemistry, clinical chemistry, natural product discovery, medicine, and metabolomics using lampreys as a model animal.

biochemistry↗

bioRxiv2022

Programming super DNA-enzyme molecules for on-demand enzyme activity modulation

Dynamic interactions of enzymes, including programmable configuration and cycling of enzymes, play important roles in the regulation of cellular metabolism. Here, we construct a super DNA-enzymes molecule (SDEM) that comprises at least two cascade enzymes and linked DNA strands to control and detect metabolism. We find that the programmable SDEM which comprises glucose oxidase (GOx) and horseradish peroxidase (HRP) has a 50-fold lower detection of limit and a 1.6-fold higher reaction rate than free enzymes. SDEM can be assembled and disassembled using a hairpin structure and a displacement DNA strand to complete multiple cycles. An entropically driven catalytic assembly (catassembly) enables different SDEMs to switch from SDEM with GOx and HRP cascades to SDEM with sarcosine oxidase (SOX) and HRP cascades by over six orders of magnitude less time than no catassembly to detect different metabolisms (glucose and sarcosine) on demand.

biochemistry↗

bioRxiv2021

Chasing the metabolism of novel syntrophic acetate-oxidizing bacteria in thermophilic methanogenic chemostats

BackgroundAcetate is the major intermediate of anaerobic digestion of organic waste to CH4. In anaerobic methanogenic systems, acetate degradation is carried out by either acetoclastic methanogenesis or a syntrophic degradation by a syntrophy of acetate oxidizers and hydrogenotrophic methanogens. Due to challenges in isolation of syntrophic acetate-oxidizing bacteria (SAOB), the diversity and metabolism of SAOB, as well as the mechanisms of their interactions with methanogenic partners remain poorly understood. ResultsIn this study, we successfully enriched previously unknown SAOB by operating continuous thermophilic anaerobic chemostats fed with acetate, propionate, butyrate, or isovalerate as the sole carbon and energy source. They represent novel clades belonging to Clostridia, Thermoanaerobacteraceae, Anaerolineae, and Gemmatimonadetes. In these SAOB, acetate is degraded through reverse Wood-Ljungdahl pathway or an alternative pathway mediated by the glycine cleavage system, while the SAOB possessing the latter pathway dominated the bacterial community. Moreover, H2 is the major product of the acetate degradation by these SAOB, which is mediated by [FeFe]-type electron-confurcating hydrogenases, formate dehydrogenases, and NADPH reoxidation complexes. We also identified the methanogen partner of these SAOB in acetate-fed chemostat, Methanosarcina thermophila, which highly expressed genes for CO2-reducing methanogenesis and hydrogenases to supportively consuming H2 at transcriptional level. Finally, our bioinformatical analyses further suggested that these previously unknown syntrophic lineages were prevalent and might play critical roles in thermophilic methanogenic reactors. ConclusionThis study expands our understanding on the phylogenetic diversity and in situ biological functions of uncultured syntrophic acetate degraders, and presents novel insights on how they interact with their methanogens partner. These knowledges strengthen our awareness on the important role of SAO in thermophilic methanogenesis and may be applied to manage microbial community to improve the performance and efficiency of anaerobic digestion.

microbiology↗

bioRxiv2021

Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells

PCOS is typically characterized by polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes, however, poor quality of oocytes lead to lower fertilization and implantation rates, decreased pregnancy and increased miscarriage rates. Our study suggests that global gene expression and cell to cell interactions of oocytes and CCs are significantly altered in women with PCOS. Noticeably, genes related to microtubules such as TUBB8 and TUBA1C are abnormally highly expressed in PCOS oocytes, reducing oocyte quality. The pattern of transposable element expression distinguishes PCOS from Control oocytes, implying the role of transposable elements in the occurrence of PCOS.

cell biology↗