近日，中国科学院微生物研究所王硕及其团队的研究认为先天淋巴样细胞前体的表观遗传印迹指导先天淋巴样细胞的谱系分离。相关论文于2025年9月18日发表在《自然—免疫学》杂志上。

在这里，该研究团队同时分析了ILC亚群和ILC前体（ILCPs）的单细胞DNA甲基组、染色质可及性和转录组，发现ILCPs可以分为两个亚群（ILCP1和ILCP2）。ILCP2s具有高度异质性的DNA甲基化谱，根据其DNA甲基化特征可分为三组，这与ILC亚群的DNA甲基化特征相匹配。研究团队鉴定了每个ILC子集的特征甲基化区域（SMRs），并追踪了ILCP分化过程中的DNA甲基化印记。具有ILC亚群低甲基化SMRs特征的ILCP2s分化为这些亚群。SMRs的DNA甲基化编辑抑制了ILC谱系分离，而在ILCPs中删除Dnmt1则取消了SMRs的异质性分布，导致ILC分化缺陷。这些发现为表观遗传印迹决定免疫细胞发育过程中的谱系分离提供了证据。

据了解，先天淋巴样细胞（ILCs）对粘膜稳态至关重要，但其谱系分离的表观遗传调控仍然是未知的。

附：英文原文

Title: Epigenetic imprinting in innate lymphoid cell precursors directs the lineage segregation of innate lymphoid cells

Author: Liu, Zhen, Shao, Fei, Zhang, Qiang, Zhao, Min, Gao, Shuai, Zhang, Xusheng, Yu, Dou, Zhang, Jingyao, Xia, Pengyan, Wang, Shuo

Issue&Volume: 2025-09-18

Abstract: Innate lymphoid cells (ILCs) are essential for mucosal homeostasis, but the epigenetic regulation of their lineage segregation remains elusive. Here we simultaneously profiled the single-cell DNA methylome, chromatin accessibility and transcriptome of ILC subsets and ILC precursors (ILCPs) and found that ILCPs could be divided into two subgroups (ILCP1 and ILCP2). ILCP2s had highly heterogeneous DNA methylation profiles and could be divided into three groups according to their DNA methylation characteristics, which matched those of ILC subsets. We identified the signature methylation regions (SMRs) of each ILC subset and traced the DNA methylation imprinting during ILCP differentiation. ILCP2s with hypomethylated SMRs characteristic of ILC subsets differentiated into those subsets. DNA methylation editing of SMRs suppressed ILC lineage segregation, while deletion of Dnmt1 in ILCPs abrogated the heterogeneous distribution of SMRs and resulted in ILC differentiation defects. These findings provide evidence that epigenetic imprinting determines lineage segregation during immune cell development.

DOI: 10.1038/s41590-025-02261-0

Source: https://www.nature.com/articles/s41590-025-02261-0