Spatial transcriptomics of human FALD and normal livers
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE306111 | GEO | 2026/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Spatial transcriptomics of human FALD and normal livers
| PRJNA1309137 | ENA
Project description:scRNA-seq was performed on Fontan-associated liver disease (FALD) and normal livers using 10x Genomics Fixed RNA Profiling. The expression of connective tissue growth factor (CTGF) was upregulated in the EC cluster in the FALD livers. The scRNA-seq analysis also showed that the integrin signaling pathway was activated and the expression of YAP/TAZ target genes was upregulated in the EC cluster in the FALD livers.
2026-03-01 | GSE291325 | GEO
Project description:Background: Fontan-associated liver disease (FALD) is a common sequelae of single-ventricle patients palliated with the Fontan operation. FALD severity can impact clinical decisions; however, the pathophysiology of FALD progression is unknown. Methods: Single-cell spatial transcriptomics (ST) was performed on liver explant tissue sections from FALD patients with early and advanced fibrosis using CosMxTM Spatial Molecular Imaging with in-situ hybridization of 6000 genes (n=2). Immunofluorescence for hepatic zonation and cellular stress markers was used to confirm protein expression based on ST analysis in biopsy and explant FALD tissues (n=17). Results: Unbiased clustering yielded 12 liver cell types, comprising five subtypes of hepatocytes. FALD with advanced fibrosis demonstrated the expansion of mid-zonal hepatocytes, accompanied by the loss of metabolic markers associated with canonical pericentral and periportal hepatocytes. Advanced FALD hepatocytes uniquely demonstrated increased cellular stress and a redundant metabolic phenotype. Advanced FALD hepatocytes changed into a senescent-like state, which we have termed hepatocyte metabolic exhaustion. Protein expression analysis confirmed metabolic exhaustion within hepatocytes and upregulation of cellular stress markers in advanced FALD tissue specimens. Immunofluorescence staining of FALD samples demonstrated a disruption of zonation and a significant increase in heat shock protein 70 (HSP70). HSP70 expression strongly correlated with the congestive hepatic fibrosis (CHF) score. Conclusions: Single-cell ST has identified a population of hepatocytes with features of metabolic exhaustion and cellular stress unique to advanced FALD.
2026-02-04 | GSE310443 | GEO
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) liver biopsies were analyzed using spatial single-cell transcriptomics (CosMx Spatial Molecular Imager, NanoString) to elucidate molecular alterations associated with hepatic fibrosis morphology, as quantified by the artificial intelligence-based FibroNest algorithm (PharmaNest). This analysis identified distinct morphological fiber phenotypes (FibroPCs), among which FibroPC4, characterized by reticular fiber structures, was associated with a hepatic stellate cell (HSC) phenotype that promotes hepatocellular carcinoma (HCC). This HCC-promoting HSC phenotype was driven by insulin-like growth factor-binding protein 7 (IGFBP-7) secreted from senescent periportal endothelial cells.
2025-08-20 | GSE292268 | GEO
Project description:<p>BACKGROUND: Single ventricle congenital heart disease (SVCHD) is a severe form of cardiac malformation in which there is only one functional ventricle. The Fontan operation is the current standard of care for SVCHD. Almost all patients who have undergone the Fontan operation develop liver fibrosis at a young age, resulting in a condition known as Fontan-associated liver disease (FALD). The pathogenesis and mechanisms underlying FALD remain little understood, hindering development of effective therapies.</p><p>OBJECTIVES: We aimed to present a comprehensive multiomic analysis of human FALD, thereby revealing the fundamental biology and pathogenesis of FALD. </p><p>METHODS: We recently generated a single-cell transcriptomic and epigenomic atlas of human FALD using snRNA-ATAC-seq, which revealed profound metabolic reprogramming in FALD. Here we applied liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics to unveil the metabolomic landscape of human FALD, using liver samples/biopsies from age and gender-matched healthy donors and FALD patients (n=12 per group). Extracted liver metabolites were analyzed by C18 high performance liquid chromatography (HPLC) and hydrophilic interaction chromatography (HILIC) followed by high resolution MS on Orbitrap. Statistical and bioinformatics analyses were performed to identify altered metabolites and metabolic pathways in FALD. These results were integrated with recently published snRNA-ATAC-seq and serum metabolomics datasets to present a comprehensive multiomic atlas of FALD. </p><p>RESULTS: We discovered profound metabolic abnormalities in livers of patients with early-stage FALD, particularly amino acid metabolism, peroxisomal fatty acid oxidation, cytochrome P450 system, glycolysis, TCA cycle, ketone body metabolism and bile acids metabolism. Integrated analyses with liver snRNA-ATAC-seq and serum metabolomics data unveiled the transcriptional mechanisms driving this metabolic reprogramming and the crosstalk between liver and the rest of the body. Comparison with human metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) revealed dysregulated amino acid metabolism as a common metabolic abnormality. </p><p>CONCLUSIONS: Our comprehensive multiomic atlas of human FALD reveals the fundamental biology and pathogenesis mechanisms of FALD.</p>
2024-12-13 | MTBLS10782 | MetaboLights
Project description:Liver biopsy samples were from patients with Fontan circulation (FC) and healthy patients undergoing resection or transplant for hepatoblastoma. We used snRNA-ATAC-seq to generate the transcriptomic and epigenomic atlas of human FALD.
2024-01-24 | GSE223843 | GEO
Project description:Spatial heterogeneity and plasticity of the mammalian liver is critical for systemic metabolic homeostasis in response to fluctuating nutritional status. Here, we generated a high-resolution transcriptomic landscape of the livers from mice that were either fed chow (fed), fasted for 18 h (fasted), or fasted for 18 h and then refed for 6 h (refed) using spatial transcriptomics (ST) and quantified changes in gene expression. This work provides a critical foundation for future mechanistic studies of liver metabolic heterogeneity and plasticity, and will help to understand the zonated pathology during liver disease progression.
2023-01-12 | GSE222796 | GEO
Project description:Spatial landscapes of the fed, fasted and refed livers from C57BL/6J mice - spatial transcriptomics
| PRJNA923378 | ENA
Project description:scRNA-seq analysis of liver constituent cells from human FALD and normal livers
| PRJNA1232820 | ENA
Project description:Purpose: Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVOTM) with spatial biology readouts to directly assess drug effects in patient tumors in situ. Patients and Methods: In a first-of-its-kind Phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation Activating Enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC). Patients scheduled for tumor resection received percutaneous intratumor injections of subasumstat and vehicle control 1 to 4 days prior to surgery, resulting in spatially localized and graded regions of drug exposure (~1000-2000 microns in diameter). Drug-exposed (n=214) and unexposed regions (n=140) were compared 2 by GeoMx Digital Spatial Profiler, with evaluation at single cell resolution in a subset of these by CosMx Spatial Molecular Imager. Results: Localized regions of subasumstat exposure revealed SUMO pathway inhibition, elevation of Type I interferon (IFN-I) response, and inhibition of cell cycle across all tumor samples. Single cell analysis by CosMx demonstrated cell cycle inhibition specific to the tumor epithelium, and IFN pathway induction commensurate with a TME shift from immune- suppressive to immune-permissive. Conclusions: Pairing CIVO with spatial profiling enabled detailed investigation of response to subasumstat across a diverse sampling of native and intact TMEs. We demonstrate that drug mechanism of action can be directly evaluated in a spatially precise manner in the most translationally relevant setting: an in situ human tumor.
2023-06-28 | GSE235475 | GEO