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Mid-Lobular Hepatocytes Exhibit Transient Proliferation Pause and Stress Response through Atf4-Ddit3 axis in Early Acute Liver Injury (10x Visium)

GSE272564 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/09/17 Platform GPL24247
Summary
Liver zonation remains a critical aspect of understanding its response to acute injury. This study investigates the impact of acetaminophen-induced acute liver injury on zonal heterogeneity during early phases of injury. Through Ki67 staining, we observed a transient pause in proliferation specifically among mid-lobular hepatocytes during the initiation phase. Using spatial transcriptomics, immunostaining, and in vivo assays, we elucidated that mid-lobular hepatocytes upregulate the Atf4-Ddit3 axis, offering temporary protection at the cost of reduced proliferation mediated by Btg2. Our findings underscore the unique zonal metabolism of acetaminophen as a determinant of differential tissue responses across lobular regions. This study highlights how distinct liver zones exhibit varied responses during the early stages of acute injury, with mid-lobular hepatocytes showing an integrated stress response characterized by protective mechanisms that temporarily suppress proliferation.
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Also filed as BioProject PRJNA1137353 and SRA study SRP520809. Searching any of these in the dataset finder brings you back here.

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