A Spatiotemporal Atlas of Mouse Liver
Understanding liver regeneration is crucial for advancements in regenerative medicine and disease research. In a groundbreaking study, researchers combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell RNA sequencing to create a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration. This research provides detailed insights into liver cell function, regeneration processes, and the intercellular communication required for tissue repair.

The study, which used a mouse model undergoing partial hepatectomy (removal of two-thirds of the liver), revealed intricate molecular gradients and gene networks that guide liver regeneration. Key findings include the identification of the transcriptional cofactor TBL1XR1, which links inflammation with Wnt/β-catenin signaling, essential for promoting hepatocyte proliferation. These insights deepen our understanding of how gene networks dynamically adjust through intercellular communication to ensure liver regeneration, even under challenging conditions.

This high-resolution study also mapped the liver’s porto-central axis, detailing the spatial organization of liver cells and their roles in maintaining liver function. The combination of Stereo-seq with single-cell transcriptomic profiling allowed researchers to explore the liver’s zonation patterns and how different cell types, including hepatocytes and non-parenchymal cells, respond to liver injury.

PackGene played a vital role in this study by providing the AAV viral particles used to investigate gene function during liver regeneration. PackGene’s contribution enabled precise manipulation of liver cells, facilitating the researchers’ ability to dissect the molecular underpinnings of liver homeostasis and regeneration.

This spatiotemporal atlas sets the stage for future research aimed at understanding organ physiology and disease mechanisms at an unprecedented level of detail. Through innovations in single-cell and spatial transcriptomics, the study opens new avenues for exploring tissue regeneration and developing therapeutic strategies for liver diseases.

Source: Xu, J., Guo, P., Hao, S. et al. A spatiotemporal atlas of mouse liver homeostasis and regeneration. Nat Genet 56, 953–969 (2024). https://doi.org/10.1038/s41588-024-01709-7.

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