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

• 成果类型: Article
• 署名作者: Labade, Ajay S.; Chiang, Zachary D.; Comenho, Caroline; Reginato, Paul L.; Payne, Andrew C.; Earl, Andrew S.; Shrestha, Rojesh; Duarte, Fabiana M.; Habibi, Ehsan; Zhang, Ruochi; Church, George M.; Boyden, Edward S.; Chen, Fei; Buenrostro, Jason D.
• 署名单位: Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8267
• DOI: 10.1126/science.adt2781
• 发表日期: 2025-07-24
• 关键词: lamin; progeria; reveals; ORGANIZATION; architecture; b1; transcription; microscopy; interior; defects

摘要

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.