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Shengli Wang

Publications and source records attributed to Shengli Wang.

2 recordsLinked to original sources
PubMed2026

Multi-omics characterization of a GPRC5A+ epithelial subpopulation associated with malignant features in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) exhibits marked cellular heterogeneity, and the cellular context of malignancy-associated epithelial programs remains incompletely defined. METHODS: We integrated 2,993 CRC samples spanning bulk RNA-seq (n = 2,568; two OS/RFS cohorts), scRNA-seq (281,961 cells/152 specimens), spatial transcriptomics (n = 6), and proteomics (n = 267). Analyses included single-cell integration/annotation, GSVA/HALLMARK, interactome, pseudotime, and ligand-receptor mapping; functional CRISPR assays, EMT immunoblotting, and xenografts; TF profiling (SCENIC/JASPAR/ChIP-qPCR); and exploratory drug-response prediction (OncoPredict), cell-sensitivity assays, and docking/MD modeling. RESULTS: We constructed a stage-stratified single-cell atlas and resolved eleven malignant epithelial subsets, characterizing Epi_4 as late-stage-enriched with EMT, hypoxia, and inflammatory programs and adverse OS/RFS. GPRC5A marked this subset, which we define as GPRC5A+Epi; its expression rose from stage I→IV and was associated with poor outcomes across cohorts, with concordant spatial/proteomic observations. GPRC5A perturbation affected CRC proliferation, migration/invasion, EMT, and xenograft tumorigenicity, supporting a functionally important role in the tested models. SCENIC and ChIP-qPCR supported FOSL1 as an upstream regulator that occupies the GPRC5A promoter. Spatial and ligand-receptor analyses predicted close association and potentially reciprocal signaling between GPRC5A+Epi and POSTN+fibroblasts (COL1A1-SDC4, COL1A1/1A2-ITGA2/ITGB1, PPIA-BSG); concurrent high GPRC5A+Epi/POSTN+Fib signatures were associated with inferior OS/RFS. Drug-response analyses identified an association between GPRC5A status and trametinib sensitivity. Docking/MD produced a computational model of a possible trametinib-GPRC5A interaction, which remains experimentally unvalidated. CONCLUSIONS: GPRC5A⁺Epi is a malignancy-associated epithelial state in CRC, and GPRC5A is functionally important for malignant phenotypes in the tested models. Its inferred relationships with POSTN⁺ fibroblasts and the trametinib findings should be regarded as hypothesis-generating pending functional crosstalk, direct-binding, and therapeutic validation.

Humans↗
PubMed2026

Biosynthesis and heterologous production of the α-agarofuran scaffold of Celangulin V from Celastrus angulatus.

Celangulin V is a widely used biopesticide derived from Celastrus angulatus, and features antifeedant and insecticidal properties as a dihydro-β-agarofuran (DHβAF) sesquiterpenoid. Its biosynthesis remains largely unexplored. Here, we assemble a chromosome-level and haplotype-resolved reference genome of C. angulatus, with each haplotype assembled into 23 pseudochromosomes and achieving scaffold N50 of 14.31 and 14.01 Mb, respectively. This high-quality genome reveals that a recent β whole-genome triplication (β-WGT) event occurred ~34.3 million years ago, and that the expansion of sesquiterpene synthases and cytochrome P450s from the CYP71BE family results from whole-genome duplication (WGD) event and tandem duplication, respectively. We identify CaTPS16 as a γ-eudesmol synthase, and show that CYP71BE416 further catalyzes the γ-eudesmol to tetrahydrofuran ring α-agarofuran for Celangulin V biosynthesis. We further achieve the de novo synthesis of α-agarofuran in Saccharomyces cerevisiae through combined coexpression of these genes. This study has significantly increases the available genomic resources of the Celastraceae family, improves our understanding of the biosynthetic origins and evolution of the tetrahydrofuran ring in DHβAF sesquiterpenoids, and enables its heterologous bioproduction in microbial chassis.

Celastrus↗