Biomedical subjects

Quanhu Sheng

Publications and source records attributed to Quanhu Sheng.

4 recordsLinked to original sources

PubMed2026

An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations.

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts (myCAFs) that are intimately associated with invasive tumor cells and correlate with poor prognosis, lymph node metastasis, and disease progression in thyroid carcinoma. We also revealed a population of inflammatory CAFs that are distant to tumor cells and are found in the inflammatory stromal microenvironment of autoimmune thyroiditis. Together, our study provides spatial profiling of thyroid cancer evolution in samples with mixed WDTC/ATC histopathology and identifies a prognostic myCAF subtype with potential clinical utility in predicting aggressive disease in both children and adults.

Humans↗

PubMed2025

A comprehensive analysis of supermere, exomere, and extracellular vesicle isolation and cargo in colorectal cancer.

Biofluids contain a heterogeneous mixture of extracellular vesicles and non-vesicular nanoparticles (including exomeres and supermeres) that transport a diverse array of proteins, RNA, and lipids. Our previous efforts to characterize the contents of these carriers in colorectal cancer relied on 2D culture systems requiring large-scale setups and time-consuming ultracentrifugation-based isolation. To streamline this process, we have combined 3D hollow-fiber bioreactor production and fast-protein liquid chromatography-based size-exclusion chromatography. Here, we compare the impact of culture methods and purification strategies on small extracellular vesicle, exomere, and supermere cargo. Proteomic analyses show consistently distinct profiles for extracellular vesicles, exomeres, and supermeres regardless of culture conditions or isolation method. In contrast, these two variables influence small RNAs, their base modifications, and lipidomic profiles. We present an online tool to query these and future secretome datasets (https://superomics.shinyapps.io/browse).

Humans↗

PubMed2025

A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.

Transfer RNA-derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3'tDR, a hypoxia-induced tDR derived from the 3' end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3'tDR. Mechanistically, tRNA-Asp-GTC-3'tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3'tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Animals↗

PubMed2025

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs (p < 5 × 10-8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.

Humans↗