研究团队描述了扩展原位基因组测序（ExIGS），这是一种能够测序基因组DNA和超分辨率定位单细胞核蛋白的技术。将ExIGS应用于早衰性成纤维细胞表明，纤层蛋白异常与可能侵蚀细胞身份的异常染色质调节热点有关。研究发现，核纤层蛋白通常会抑制转录，这表明核形态的变化可能会影响组织和衰老细胞的基因调控。这些结果表明，ExIGS可以作为一个将核异常与基因调控联系起来的通用平台，为疾病机制提供见解。
据了解，显微镜学和基因组学的主题是表征细胞功能，但方法连接这两种类型的信息是缺乏的，特别是在亚核分辨率。
附：英文原文
Title: Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation
Author: Ajay S. Labade, Zachary D. Chiang, Caroline Comenho, Paul L. Reginato, Andrew C. Payne, Andrew S. Earl, Rojesh Shrestha, Fabiana M. Duarte, Ehsan Habibi, Ruochi Zhang, George M. Church, Edward S. Boyden, Fei Chen, Jason D. Buenrostro
Issue&Volume: 2025-05-29
Abstract: 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 superresolution 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 variation in nuclear morphology may affect gene regulation across tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform to link nuclear abnormalities to gene regulation, offering insights into disease mechanisms.
DOI: adt2781
Source: https://www.science.org/doi/10.1126/science.adt2781