2025/05/29 by Ajay S. Labade, Zachary Chiang, Caroline Comenho +11 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #RNA Research and Splicing #Nuclear Structure and Function
paper · doi:10.1126/science.adt2781
openalex publication_date 2025/05/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.