Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation

作者：Ajay S. Labade, Zachary Chiang, Caroline Comenho, Paul Reginato, Andrew C. Payne, Andrew Earl, Rojesh Shrestha, Fabiana M. Duarte, Ehsan Habibi, Ruochi Zhang, George M. Church, Edward S. Boyden, Fei Chen, Jason D. Buenrostro · 发表于：Science · 年份：2025 · DOI：10.1126/science.adt2781 · 被引用次数：11 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、Nuclear Structure and Function

Microscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and super-resolution localization of nuclear proteins in single cells. Applying ExIGS to progeria-derived fibroblasts revealed that lamin abnormalities are linked to hotspots of aberrant chromatin regulation that may erode cell identity. Lamin was found to generally repress transcription, suggesting that variation in nuclear morphology may affect gene regulation across tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform with which to link nuclear abnormalities to gene regulation, offering insights into disease mechanisms.