Скачать или смотреть Your Cell's Nuclear Shape: A Hidden Clue to Disease? [Science, 2025]

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Pathologists have long used odd nuclear shapes—like blebs or "wrinkled" lamina—as visual clues for disease and aging, but connecting these shapes to specific gene misregulation in the same cell has been a persistent mystery. New research published in Science introduces a groundbreaking technology: "Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation". This pivotal study, led by Ajay S. Labade†, Zachary D. Chiang†, Caroline Comenho†, and Jason D. Buenrostro*, along with their collaborators, is accessible at https://doi.org/10.1126/science.adt2781.
ExIGS (Expansion in situ genome sequencing) is a novel platform that finally bridges the gap between a "funny-looking nucleus" and the broken regulatory circuits inside it. By physically expanding tissue and capturing barcoded DNA, ExIGS can assign base-resolved genomic reads back to their precise sub-nuclear locations. This allows scientists to directly see how nuclear architecture, like blebs or invaginations, influences local chromatin organization and gene expression. Applied to progeria, ExIGS revealed local hotspots of aberrant chromatin regulation linked to lamin defects, showing that lamin structures are generally associated with transcriptional repression. This sheds light on how nuclear contour changes could predict crucial changes in genome accessibility, impacting aging, cancer, and rare laminopathies.
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