Biomedical subjects

Tao Liu

Publications and source records attributed to Tao Liu.

12 recordsLinked to original sources

PubMed2026

Metabolic depot for nucleated erythrocyte degradation: molecular and structural elucidation of the teleost melanomacrophage center.

The function of melanomacrophage centers (MMCs) has long been controversial. While their foundational function is widely accepted as "metabolic dumps" for waste processing, a widely circulated hypothesis posits that they are primitive germinal centers (GCs) executing adaptive immunity. To elucidate this controversy, this study systematically evaluated the splenic MMCs in a higher teleost ( Micropterus salmoides) by combining transmission electron microscopy (TEM) and high-resolution spatial transcriptomics. Structurally, TEM revealed that the MMC comprises a core with characteristic sparse cellular density, filled with cellular debris and encapsulated by a fibrous layer. Molecularly, under physiological conditions, MMC regions exhibited low transcriptional activity. We did not detect clear enrichment of B cell and T cell lineage genes, and the key GC marker aicda was not observed. Conversely, its predominant molecular signature was characterized by macrophage-driven iron metabolism (e.g., ferritin) and erythrocyte degradation (e.g., hba1). Furthermore, the physicochemical properties of MMCs pigments (e.g., argyrophilia) suggest that traditional histological staining methods warrant cautious interpretation regarding potential non-specific signals. In conclusion, our findings characterize the MMC as a highly specialized metabolic processing and sequestration niche. This study provides new perspectives on the evolution of immune-metabolic homeostasis in poikilothermic vertebrates, advances comparative immunology, and offers a critical scientific reference for the accurate interpretation of MMCs as a biological indicator in pathology and ecotoxicology.

Animals↗

PubMed2026

Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets.

High-grade gliomas (HGGs) in children and adolescents and young adults (AYA) exhibit distinct biology across the neurodevelopmental spectrum. To dissect tumor-intrinsic molecular characteristics independent of developmental variation, we perform comprehensive proteogenomic analyses of tumors from 112 HGG patients aged 0-40 years. Our multi-omics analysis identifies two AYA subgroups-adolescents (aged 15-26 years) and young adults (aged 26-40 years)-with distinct molecular profiles and survival outcomes. Tumor-normal comparisons and survival modeling highlight roles of oxidative phosphorylation and neuronal system biology in glioma progression. Causal network analysis and cell line studies provide a rationale for personalized therapies targeting candidate kinases, such as CDK8. Survival modeling, clustering, and immune-landscape analyses identify proteins, post-translational modifications, and immune signatures linked to outcomes and reveal clinically relevant differences between male and female patients.

adolescent and young adult glioma↗

PubMed2026

MACS3: A Peak-calling Platform for Bulk and Single-cell Regulatory Genomics.

Since the original publication of Model-based Analysis for ChIP-Seq (MACS), the software has been widely used to identify enriched genomic regions in ChIP-seq, ATAC-seq, CUT&RUN, DNase-seq, and related regulatory genomics assays. Over the years, MACS has evolved substantially, with MACS version 3 (MACS3) now serving as the actively maintained implementation. MACS3 preserves the core MACS framework for fragment pileup, dynamic local background noise, statistical enrichment testing, and peak refinement, while adding functionality needed for contemporary bulk and single-cell workflows. It supports conventional bulk peak calling, paired-end and fragment-based file formats, modular signal processing, direct analysis of single-cell ATAC-seq fragment files, barcode-restricted pseudobulk and cluster-level peak calling, specialized ATAC-seq and variant-calling modules, as well as command-line and programmatic interfaces. MACS3 is distributed through standard software channels and supported by continuous testing across operating systems, Python versions, and CPU architectures. Here we describe the architecture, current capabilities, and recommended use of MACS3, providing an updated reference for applying the MACS framework in contemporary bulk and single-cell regulatory genomics workflows. MACS3 is open-source software available at https://github.com/macs3-project/MACS.

Bioinformatics software↗

PubMed2026

Transcriptomic analysis provides molecular insights into the innate immune defense of Mactra veneriformis against Vibrio alginolyticus infection.

Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.

Animals↗

PubMed2025

Altered ruminal microbiome tryptophan metabolism and their derived 3-indoleacetic acid inhibit ruminal inflammation in subacute ruminal acidosis goats.

BACKGROUND: Subacute ruminal acidosis (SARA) is a digestive disorder that often severely jeopardizes the health and lactation performance of ruminants fed a high-energy diet. Different dairy ruminants exhibit varying degrees of inflammation accompanied by variations in the rumen microbiota when SARA occurs. Our understanding of the occurrence of SARA and varying degrees of rumen epithelial inflammation is lacking. Hence, we performed rumen metagenomic, metagenome-assembled genome and metabolomic analyses, with transcriptome and single-nucleus RNA sequence analyses, to explore the microbial mechanism of SARA occurrence and different degrees of inflammation. RESULTS: A total of 36 goats fed two diets with gradually increasing levels of rumen-degradable starch (RDS) were included in this study, and SARA goats fed 70% concentrate diets supplemented with whole corn (HGW-SARA) and SARA goats fed 70% concentrate diets supplemented with crushed corn (HGC-SARA) were identified. Moreover, 11 goats fed a control basal diet, named LGW-CON, were also included. Compared with those in the LGW-CON group, the rumen fermentation capacity was enhanced, accompanied by ruminal epithelial and systemic inflammation, in goats from HGW-SARA and HGC-SARA. Between them, HGC-SARA goats presented less inflammation. Notably, the ruminal inflammation-related pathways were increased only in the HGW-SARA group but not in the HGC-SARA group. Metagenomic analysis revealed that the β diversity of SARA goats was significantly different from that of LGW-CON goats. Ruminococcus significantly increased in both SARA groups, whereas Prevotella and Bacteroidales significantly decreased, which was accompanied by a decrease in cellulose and hemicellulose enzymes and an increase in lysozymes and lipopolysaccharide synthesis enzymes. Multi-omics analysis of the ruminal contents and tissues suggested that epithelial inflammation was caused by disturbed ruminal microbiome-induced Th17 cell differentiation and IL-17 signalling pathway activation. Comparative analyses between the HGW-SARA and HGC-SARA groups highlighted the importance of Selenomonas and Bifidobacterium, as well as bacterial tryptophan metabolism, in the production of 3-indoleacetic acid, which mitigated ruminal epithelial inflammation by modulating Th17 cells and inhibiting IL-17 signalling. Ruminal microbiota transplantation from HGW-SARA goats to healthy dairy goats and mice revealed the role of microbes in epithelial inflammation. Additionally, 3-indoleacetic acid supplementation reduced rumen inflammation and the IL-17 concentration in the serum, improved VFAs absorption, and enhanced milk production. CONCLUSIONS: This study unveiled that after SARA was induced by high-concentrate feeding, the rumen homeostasis was disrupted, and rumen fiber degradation capacity of dairy goats decreased, but the LPS synthesis capacity increased, and inflammation of the rumen epithelium was observed. However, the ruminal microbial species from the Bifidobacterium and Selenomonas genera and bacterial 3-indole acetic acid are pivotal in mitigating ruminal epithelial inflammation during SARA in dairy goats. This could potentially be attributed to the modulation of ruminal Th17 cell proportions and the inhibition of IL-17 signalling pathways. Video Abstract.

Rumen↗

PubMed2025

Investigating the molecular mechanisms, drug prediction, and validation of CCNA2 and MAD2L1 in esophageal squamous cell carcinoma based on bioinformatics.

OBJECTIVE: Aims to comprehensively investigate the expression patterns of CCNA2 and MAD2L1 in esophageal squamous cell carcinoma using bioinformatics methods. METHODS: Based on WGCNA analysis of gene mutation expression, methylation level distribution, mRNA expression and ESCC-related genes in public databases, were employed for investigating potential biomarkers for prognosis of esophageal squamous cell carcinoma(ESCC).Finally,. performing qRT-PCR and immunohistochemistry to validate. RESULTS: Ultimately identified 4 hub genes: CDK1, CCNA2,TOP2A and MAD2L1. Bioinformatics analysis showed high expression of these four genes in ESCC (P < 0.05). CCNA2 and MAD2L1 were selected for subsequent analysis based on literature.3.Single gene enrichment analysis revealed significant enrichment of CCNA2 and MAD2L1 in pathways related to splicing, bladder cancer, non-homologous end joining and homologous recombination, glycosaminoglycan biosynthesis chondroitin sulfate, progesterone-mediated oocyte maturation and mismatch repair. PASTAA database indicated the involvement of transcription factors such as Roralpha1, Pou6f1, Roralpha2, Atf-1, Pax-3, C/ebpalpha, Nkx2-1 in the regulation of CCNA2, while no transcription factors were predicted for MAD2L1..Immune infiltration analysis revealed a close association between ESCC and plasma cells, CD8 + T cells, monocytes, M0 macrophages, M1 macrophages, dendritic cells, and resting mast cells.Drug prediction for CCNA2 included 7 drugs such as ETHINYL ESTRADIOL, Seliciclib and TAMOXIFEN, while no drugs were predicted for MAD2L1.qRT-PCR and immunohistochemistry demonstrated high expression of CCNA2 in ESCC, while MAD2L1 showed no significant difference between ESCC and normal esophageal squamous epithelial tissues. CONCLUSION: CCNA2 and MAD2L1 may be potential biomarkers for ESCC, providing a novel basis for understanding the molecular mechanisms underlying ESCC pathogenesis.Additionally, the potential drugs predicted for CCNA2 may emerge as a new hope for ESCC patients in the future.

Humans↗

PubMed2025

Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.

Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate. The findings provide strong evidence that imprinting abnormalities are a primary barrier to unisexual reproduction in mammals. Moreover, this approach can significantly improve developmental outcomes for embryonic stem cells and cloned animals, opening promising avenues for advancements in regenerative medicine.

Animals↗

PubMed2025

Mutation of strigolactone biosynthetic gene DWARF 17 impairs the responses of rice tillering to N supply.

Tiller number is one important parameter for rice yield and is influenced by both strigolactone (SL) and nitrogen (N). However, how SL and N interact to regulate the tiller outgrowth in rice is unclear. In this study, we isolated a multi-tillering mutant, tin, from an ethyl methanesulfonate (EMS)-mutagenized population of Wuyunjing 7, a japonica cultivar. The tin mutant exhibited low sensitivity to varying N concentrations during the tiller development. Through bulk segregation analysis (BSA), we identified a missense mutation located in the exon of DWARF 17 (D17), a key gene involved in SL biosynthesis. Complementation experiments confirmed that D17 is responsible for the tin tiller phenotype, and exogenous application of the SL analogue GR24 restored the tiller response of tin to N. Transcriptome analysis further revealed that D17 and SL regulate the tiller response to N by modulating the expression of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes and ammonium transporter genes. These findings elucidate the mechanism by which SL and N coordinate to regulate rice tillering growth, providing valuable insights for optimizing rice plant architecture to enhance yield potential.

Oryza↗

PubMed2024

Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-Treated Pancreatic Beta Cells.

Studying regulation of protein function at a systems level necessitates an understanding of the interplay among diverse posttranslational modifications (PTMs). A variety of proteomics sample processing workflows are currently used to study specific PTMs but rarely characterize multiple types of PTMs from the same sample inputs. Method incompatibilities and laborious sample preparation steps complicate large-scale physiological investigations and can lead to variations in results. The single-pot, solid-phase-enhanced sample preparation (SP3) method for sample cleanup is compatible with different lysis buffers and amenable to automation, making it attractive for high-throughput multi-PTM profiling. Herein, we describe an integrative SP3 workflow for multiplexed quantification of protein abundance, cysteine thiol oxidation, phosphorylation, and acetylation. The broad applicability of this approach is demonstrated using cell and tissue samples, and its utility for studying interacting regulatory networks is highlighted in a time-course experiment of cytokine-treated β-cells. We observed a swift response in the global regulation of protein abundances consistent with rapid activation of JAK-STAT and NF-κB signaling pathways. Regulators of these pathways as well as proteins involved in their target processes displayed multi-PTM dynamics indicative of complex cellular response stages: acute, adaptation, and chronic (prolonged stress). PARP14, a negative regulator of JAK-STAT, had multiple colocalized PTMs that may be involved in intraprotein regulatory crosstalk. Our workflow provides a high-throughput platform that can profile multi-PTMomes from the same sample set, which is valuable in unraveling the functional roles of PTMs and their co-regulation.

Proteomics↗

PubMed2024

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma.

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, the specific roles and molecular mechanisms of SPDL1 in esophageal squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed to investigate the expression levels of SPDL1 in ESCC via transcriptome analysis using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Moreover, the biological roles, molecular mechanisms, and protein networks involved in SPDL1 were identified using machine learning and bioinformatics. The cell counting kit-8 assay, EdU staining, and transwell assay were used to investigate the effects of inhibiting SPDL1 expression on ESCC cell proliferation, migration, and invasion. Finally, the correlation between the SPDL1 expression and cancer immune infiltrating cells was evaluated by analyzing data from the TCGA database. Results showed that SPDL1 was overexpressed in the ESCC tissues. The SPDL1 expression was related to age in patients with ESCC. The SPDL1 co-expressed genes included those involved in cell division, cell cycle, DNA repair and replication, cell aging, and other processes. The high-risk scores of SPDL1-related long non-coding RNAs were significantly correlated with overall survival and cancer progression in patients with ESCC (P < 0.05). Inhibiting the SPDL1 expression was effective in suppressing the proliferation, migration, and invasion of ESCC TE-1 cells (P < 0.05). The overexpression of SPDL1 was positively correlated with the levels of Th2 and T-helper cells, and was negatively correlated with the levels of plasmacytoid dendritic cells and mast cells. In conclusion, SPDL1 was overexpressed in ESCC and was associated with immune cells. Further, inhibiting the SPDL1 expression could effectively slow down cancer cell growth and migration. SPDL1 is a promising biomarker for treating patients with ESCC.

Humans↗

PubMed2024

A novel variant in the SPTB gene underlying hereditary spherocytosis and a literature review of previous variants.

BACKGROUND: Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology. METHODS: The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. RESULTS: A novel variant (c.301-2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301-2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. CONCLUSION: We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.

Humans↗

PubMed2024

A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on Juvenile arthritis risk haplotypes.

BACKGROUND: Although genome-wide association studies (GWAS) have identified multiple regions conferring genetic risk for juvenile idiopathic arthritis (JIA), we are still faced with the task of identifying the single nucleotide polymorphisms (SNPs) on the disease haplotypes that exert the biological effects that confer risk. Until we identify the risk-driving variants, identifying the genes influenced by these variants, and therefore translating genetic information to improved clinical care, will remain an insurmountable task. We used a function-based approach for identifying causal variant candidates and the target genes on JIA risk haplotypes. METHODS: We used a massively parallel reporter assay (MPRA) in myeloid K562 cells to query the effects of 5,226 SNPs in non-coding regions on JIA risk haplotypes for their ability to alter gene expression when compared to the common allele. The assay relies on 180 bp oligonucleotide reporters ("oligos") in which the allele of interest is flanked by its cognate genomic sequence. Barcodes were added randomly by PCR to each oligo to achieve > 20 barcodes per oligo to provide a quantitative read-out of gene expression for each allele. Assays were performed in both unstimulated K562 cells and cells stimulated overnight with interferon gamma (IFNg). As proof of concept, we then used CRISPRi to demonstrate the feasibility of identifying the genes regulated by enhancers harboring expression-altering SNPs. RESULTS: We identified 553 expression-altering SNPs in unstimulated K562 cells and an additional 490 in cells stimulated with IFNg. We further filtered the SNPs to identify those plausibly situated within functional chromatin, using open chromatin and H3K27ac ChIPseq peaks in unstimulated cells and open chromatin plus H3K4me1 in stimulated cells. These procedures yielded 42 unique SNPs (total = 84) for each set. Using CRISPRi, we demonstrated that enhancers harboring MPRA-screened variants in the TRAF1 and LNPEP/ERAP2 loci regulated multiple genes, suggesting complex influences of disease-driving variants. CONCLUSION: Using MPRA and CRISPRi, JIA risk haplotypes can be queried to identify plausible candidates for disease-driving variants. Once these candidate variants are identified, target genes can be identified using CRISPRi informed by the 3D chromatin structures that encompass the risk haplotypes.

Humans↗