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Spatial single-cell transcriptomics of MASLD-affected liver biopsy samples.

ABSTRACT: Spatial single-cell transcriptomics of MASLD-affected liver biopsy samples.

PROVIDER: PRJNA1237793 | ENA |

REPOSITORIES: ENA

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Spatial single-cell transcriptomics of MASLD-affected liver biopsy samples.

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

Integrated bulk and spatial transcriptomic analysis identifies progression-associated molecular signatures in biopsy-proven hypertensive nephropathy [Spatial Transcriptomics]

Project description:Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD), but molecular mechanisms underlying disease progression remain poorly understood. We aimed to identify transcriptomic signatures associated with disease progression and to localize these signatures within renal architectures. Patients with biopsy-proven HN were selected from the Norwegian Kidney Biopsy Registry and stratified after ≥5 years of follow-up into early stable (ES), early progressor (EP), late stable (LS) and late progressor (LP) based on baseline kidney function and annual eGFR decline. Bulk transcriptomic profiling was performed in a discovery cohort and validated in an independent cohort using nCounter profiling. Spatial transcriptomics was applied to map progression-associated signatures to nephron compartments. Bulk RNA sequencing identified 415 differentially expressed genes (DEGs) between ES and EP, and 692 between LS and LP samples. ES was enriched in circadian rhythm pathways, with reduced NR1D1 and NR1D2 expression in EP. LP was associated with metabolic reprogramming including glutathione, retinol and amino acid metabolism. Random forest modelling identified NR1D1 gene expression as a key classifier, validated in an independent cohort. Spatial transcriptomics revealed nephron segment-specific expression patterns, including a proximal tubule cluster enriched in ferroptosis in LP. Comparative nephron-segment analyses across groups revealed progression-associated biomarkers, including CHGA, CCN2 and SFRP2 in glomeruli, and APOE in proximal tubules. HN progression appears to involve stage-specific and compartmentalized molecular programs. Integration of bulk and spatial transcriptomics identifies candidate biomarkers and pathways, potentially supporting innovative prognostic stratification and therapeutic strategies.

2026-07-22 | GSE339455 | GEO

NanoString CosMx SMI (human) on ten human MASLD samples

Project description:CosMx SMI is a high-plex in situ analysis platform to provide spatial multiomics with formalin-fixed paraffin-embedded (FFPE) and fresh frozen (FF) tissue samples at cellular and subcellular resolution. CosMx SMI is an integrated system with mature cyclic fluorescent in situ hybridization (FISH) chemistry, high-resolution imaging readout, interactive data analysis and visualization software. Herein we used the CosMx SMI with the CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex) supplemented with 14 custom genes of interest to probe different disease stages of MASLD/MASH, previously known as NAFLD.

2025-12-18 | GSE312698 | GEO

Spatial transcriptome profile of liver tissue from a patient with metabolic dysfunction-associated steatotic liver disease

Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) causes progressive liver fibrosis and hepatocellular carcinoma (HCC). By using archived fixed surgical liver tissue affected with MASLD, we performed Visium Spatial Transcriptome profiling to study spatially-resolved moelcular dysregulatons associated with the clinical phenotypes of the disease and mechanisms of liver fibrogenesis and carcinogenesis.

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Effects of D4-MASLD and D5-MASLD Diets on Rats: Pathway Alterations Similar to Human MASLD

Project description:Animal models are essential to understand the mechanisms underlying the onset and progression of metabolic associated steatotic liver disease (MASLD), a rapidly growing form of chronic liver disease driven largely by the global rise in metabolic syndrome. However, existing animal models for MASLD often fail to accurately reproduce advanced human liver disease, and have varying degrees of clinical relevance. To address this, we have undertaken efforts to create a dietary translational model of MASLD in rats that closely replicates the full MASLD phenotype observed in humans, including advanced fibrosis, portal hypertension, and metabolic syndrome. Three MASLD rat models were developed by sequentially combining a high-fat glucose-fructose diet (HFGFD) with additional factors: lipopolysaccharide, increased cholesterol (Chol), and cholic acid (CA) at different concentrations. Of these, two diets—D4-MASLD (HFGFD + 2% Chol) and D5-MASLD (HFGFD + 2% Chol + 0.1% CA)—effectively replicated MASLD characteristics. Transcriptomic analysis revealed that while both diets significantly altered gene expression compared to controls, D5-MASLD had a greater impact on the activation of inflammation and immune response pathways. The inclusion of CA in D5-MASLD exacerbated pathways related to microbiota changes, intestinal barrier dysfunction, and bacterial translocation. Additionally, comparison of the transcriptomic profiles of these diet-induced rat models with data from MASLD/MASH patients further validated the relevance of these models, establishing a robust platform for studying MASLD pathogenesis and evaluating potential therapeutic interventions.

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Project description:These data were used in the spatial transcriptomics analysis of the article titled \\"Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging\\".

2024-04-22 | E-MTAB-13991 | biostudies-arrayexpress

Integrated bulk and spatial transcriptomic analysis identifies progression-associated molecular signatures in biopsy-proven hypertensive nephropathy [Spatial Transcriptomics]

Project description:Integrated bulk and spatial transcriptomic analysis identifies progression-associated molecular signatures in biopsy-proven hypertensive nephropathy [Spatial Transcriptomics]

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2025-04-22 | E-MTAB-13655 | biostudies-arrayexpress

Intestinal organoid expression data from patients with MASLD-cirrhosis versus non-fibrotic MASLD

Project description:This study aimed to establish and characterize an in vitro model of human intestinal organoids isolated from duodenal samples of patients with non-fibrotic MASLD and those with MASLD-cirrhosis. Whole transcriptome analysis and the energetic and redox status of the organoids were assessed to characterize intestinal functional impairment in the context of MASLD. We used microarrays to detail the whole transcriptome dysregulation underlying intestinal dysfunction in organoids isolated from chirrotic versus non-fibrotic MASLD patients.

2025-09-04 | GSE299719 | GEO

IGFBP-7 transforms hepatic stellate cells into an HCC-promoting phenotype in MASLD.

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2025-08-20 | GSE278593 | GEO

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