哺乳动物着床后胚胎和蜕膜的空间5mC-seq分析，这一成果由中国科学院生物物理研究所刘江‌小组经过不懈努力而取得。2026年4月27日出版的《自然—方法学》杂志发表了这项成果。

在这里，该研究团队开发了空间5mC-seq (SmC-seq)，这是一种基于微流体的方法，可以在接近单细胞的分辨率下提供无偏倚的全基因组甲基组。应用SmC-seq分析小鼠着床后发育，揭示了内细胞质量源性组织中DNA甲基化的明显空间异质性模式。研究组在E8.5胎盘外锥体中发现了一个具有不同甲基化和增殖状态的双层组织。

出乎意料的是，在植入后蜕膜的中间区域观察到一部分DNA甲基化水平较低的母体组织，富含营养提供者祖细胞。营养供给者祖细胞的低甲基化区域与细胞增殖有关。值得注意的是，在成熟的营养供应细胞中，与低甲基化区域相关的基因在胞吐和营养合成中富集，这与胎盘功能之前胚胎发生的营养供应有关。总之，SmC-seq实现了空间DNA甲基化定位，促进了他们对生物事件的理解。

据悉，DNA甲基化对发育和疾病至关重要，但目前还没有空间DNA甲基化分析技术的报道。

附：英文原文

Title: Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals

Author: Shan, Xun, Tang, Yimin, Hu, Jinzhou, Bian, Mingyuan, Yao, Xuelong, Gao, Lei, Liu, Jiang

Issue&Volume: 2026-04-27

Abstract: DNA methylation is vital for development and diseases, yet no spatial DNA methylation profiling technology has been reported. Here we developed spatial 5mC-seq (SmC-seq), a microfluidic-based method providing unbiased genome-wide methylome at near single-cell resolution. Applying SmC-seq to mouse post-implantation development revealed a clear spatial heterogenous pattern of DNA methylation in inner cell mass-derived tissues. We identified a two-layer organization in the E8.5 ectoplacental cone with distinct methylation and proliferation states. Unexpectedly, a portion of maternal tissue with low DNA methylation level, enriched for nutrient-supplier progenitors, is observed in the middle region of decidua post-implantation. The hypomethylated regions in the nutrient-supplier progenitor cluster are associated with cell proliferation. Notably, the genes associated with hypomethylated regions in mature nutrient-supplier cluster are enriched in exocytosis and nutrient synthesis, linked to nutrient provision for embryogenesis before placental function. In summary, SmC-seq enables spatial DNA methylation mapping, advancing our understanding of biological events.

DOI: 10.1038/s41592-026-03079-w

Source: https://www.nature.com/articles/s41592-026-03079-w