EXO - Beyond the Cell, a journal about how cells interact with their environment

Genomics Daily

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In the blink of an AI: Spotting millions of molecules inside us

Scientists at EPFL and TU Dresden have developed a new machine learning method called Spotiflow that can automatically process both 2D and 3D microscopy images with unprecedented speed and precision.

Spatial single-cell interactome and niche-specific molecular signatures in alcohol-related liver disease

Alcohol-related liver disease (ALD) remains a major global health burden with limited therapeutic options due to an incomplete understanding of its underlying molecular mechanisms and cellular crosstalk. Here, we applied ultra-high resolution (on 2μm spots) spatial transcriptomics to a cirrhotic liver tissue obtained from an end-stage ALD patient, analyzing >265,000 spatially resolved cells with further validation on single-cell and single-nuclei datasets from patients with ALD cirrhosis. Our analysis delineated distinct cellular sub-populations and molecular landscapes across fibrotic, vascular, and parenchymal niches of ALD cirrhosis. We identified robust zonation of hepatocytes, hepatic stellate cells, and diverse immune subpopulations, including enrichment of pro-inflammatory T cells and dendritic cells in the fibrotic niche and MARCO +; tissue-resident macro-phages localizing mostly in parenchymal areas. Analysis of spatial metrics assigned expression of WNT4 , RCAN3 , PPIAL4G , PLA2G5 , and SLC6A9 to the fibrotic environment in ALD. Differential expression and ligand-receptor interactome analyses revealed niche-specific signaling, with marked CCL19 - CCR7 activity in fibrotic regions and DLL4 - NOTCH3 crosstalk in vascular compartments. Notably, WNT4+; fibroblasts emerged as key mediators of extracellular matrix remodeling and chemoattraction, particularly via CCL19 -mediated signaling towards CD8 T cells, which was validated on single-cell resolution within the ALD cirrhotic liver in external datasets. These spatial and single-cell findings highlight novel potential therapeutic targets for patients with ALD cirrhosis. ### Competing Interest Statement The authors have declared no competing interest.