宾夕法尼亚大学邓彦翔小组近日取得一项新成果。经过不懈努力，他们提出了组织中DNA甲基组和转录组的空间联合分析。相关论文于2025年9月3日发表于国际顶尖学术期刊《自然》杂志上。

在这里，课题组介绍了一种在接近单细胞分辨率下对同一组织切片的DNA甲基化和转录组进行全基因组空间共谱分析的方法。将该技术应用于同母胚胎发生和出生后的同母脑，可获得丰富的DNA-RNA双峰组织图谱。这些图谱揭示了已知甲基化生物学的空间背景及其与基因表达的相互作用。这两种模式在空间模式上的一致性和区别突出了哺乳动物发育和脑功能空间规划中细胞身份的协同分子定义。

通过整合两个不同发育阶段的单主题胚胎的空间图谱，该团队重建了哺乳动物胚胎发生的表观基因组和转录组动力学，揭示了序列、细胞类型和区域特异性甲基化介导的转录调控的细节。该方法将空间组学的范围扩展到包括DNA胞嘧啶甲基化，从而能够更全面地了解组织生物学在发育和疾病中的作用。

研究人员表示，组学分析的空间分辨率是理解组织生物学的基础。DNA甲基化是一种典型的表观遗传标记，广泛涉及转录调控，但目前缺乏对DNA甲基化进行空间分析的能力。

附：英文原文

Title: Spatial joint profiling of DNA methylome and transcriptome in tissues

Author: Lee, Chin Nien, Fu, Hongxiang, Cardilla, Angelysia, Zhou, Wanding, Deng, Yanxiang

Issue&Volume: 2025-09-03

Abstract: The spatial resolution of omics analyses is fundamental to understanding tissue biology1,2,3. The capacity to spatially profile DNA methylation, which is a canonical epigenetic mark extensively implicated in transcriptional regulation4,5, is lacking. Here we introduce a method for whole-genome spatial co-profiling of DNA methylation and the transcriptome of the same tissue section at near single-cell resolution. Applying this technology to mouse embryogenesis and the postnatal mouse brain resulted in rich DNA–RNA bimodal tissue maps. These maps revealed the spatial context of known methylation biology and its interplay with gene expression. The concordance and distinction in spatial patterns of the two modalities highlighted a synergistic molecular definition of cell identity in spatial programming of mammalian development and brain function. By integrating spatial maps of mouse embryos at two different developmental stages, we reconstructed the dynamics that underlie mammalian embryogenesis for both the epigenome and transcriptome, revealing details of sequence-, cell-type- and region-specific methylation-mediated transcriptional regulation. This method extends the scope of spatial omics to include DNA cytosine methylation, enabling a more comprehensive understanding of tissue biology across development and disease.

DOI: 10.1038/s41586-025-09478-x

Source: https://www.nature.com/articles/s41586-025-09478-x