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Novoselsky, R.

Publications and source records attributed to Novoselsky, R..

2 recordsLinked to original sources

Subcellular mRNA localization patterns across tissues resolved with spatial transcriptomics

Subcellular RNA localization, including nuclear retention and apical-basal compartmentalization in polarized epithelia plays a central role in post-transcriptional regulation. However, methods for high-throughput mapping of mRNA localization within intact tissue sections remain limited. Here, we apply high-resolution spatial transcriptomics (VisiumHD) to systematically resolve intracellular mRNA localization across diverse mammalian tissues. We introduce a computational approach that extracts subcellular features from spatial data and quantifies transcript localization patterns. Using this framework, we map apical-basal mRNA localization and nuclear retention in gastrointestinal epithelia and in liver hepatocytes. Our analyses reveal conserved and tissue-specific localization signatures that can be readily obtained from standard high-definition spatial transcriptomics experiments. This approach broadens the scope of spatial transcriptomics by enabling routine investigation of intracellular RNA distributions in both healthy and diseased tissues.

systems biology↗

A spatial transcriptomics atlas of live donors reveals unique zonation patterns in the healthy human liver

Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live donors. Neurologically deceased donors often show ischemic changes, while tissues near diseased regions may have altered gene expression. The liver, with its unique regenerative capacity, allows analysis from live healthy donors (LHDs). Using spatial transcriptomics (Visum, Visium HD and MERFISH), we analyzed 16 liver samples: eight from young LHDs and eight from patients with liver pathology, sampling adjacent normal tissue. LHD livers displayed significant gene expression differences from adjacent normal tissues. Hepatocytes exhibited marked zonation along the porto-central axis of liver lobules, with key functions pericentrally shifted compared to other mammals. Our atlas identified dynamic programs in early steatotic hepatocytes, showing transitions from lipid uptake in low-lipid regions to insulin hypersensitivity in high-lipid regions. This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte adaptations in steatosis.

cell biology↗