欧洲分子生物学实验室Judith B. Zaugg小组的一项最新研究发现，单细胞超高通量多重染色质和RNA分析揭示基因调控动力学。相关论文于2025年5月26日发表在《自然—方法学》杂志上。

在这里，研究组提出了单细胞超高通量多重测序（SUM-seq），用于共同测定单核中染色质可及性和基因表达。SUM-seq能够在百万细胞规模上分析数百个样本，并且优于当前的高通量单细胞方法。该研究组证明了SUM-seq能够(1)解决巨噬细胞M1和M2极化的时间基因调控，以架起TF调控网络和免疫疾病遗传变异的桥梁；(2)定义原代辅助性T细胞亚群的调控景观；(3)通过阵列CRISPR筛选剖析干扰谱系TF对自然分化的人诱导多能干细胞的影响。SUM-seq为超高通量单细胞多组测序提供了一种具有成本效益、可扩展的解决方案，加速揭示细胞分化、对扰动的反应和疾病研究中的复杂基因调控网络。

据悉，增强子和转录因子在调节细胞过程中起着至关重要的作用。目前研究这些基因调控机制的多组学技术缺乏多路复用能力和可扩展性。

附：英文原文

Title: Single-cell ultra-high-throughput multiplexed chromatin and RNA profiling reveals gene regulatory dynamics

Author: Lobato-Moreno, Sara, Yildiz, Umut, Claringbould, Annique, Servaas, Nila H., Vlachou, Evi P., Arnold, Christian, Bauersachs, Hanke Gwendolyn, Campos-Forns, Vctor, Kim, Minyoung, Berest, Ivan, Prummel, Karin D., Noh, Kyung-Min, Marttinen, Mikael, Zaugg, Judith B.

Issue&Volume: 2025-05-26

Abstract: Enhancers and transcription factors (TFs) are crucial in regulating cellular processes. Current multiomic technologies to study these elements in gene regulatory mechanisms lack multiplexing capability and scalability. Here we present single-cell ultra-high-throughput multiplexed sequencing (SUM-seq) for co-assaying chromatin accessibility and gene expression in single nuclei. SUM-seq enables profiling hundreds of samples at the million cell scale and outperforms current high-throughput single-cell methods. We demonstrate the capability of SUM-seq to (1) resolve temporal gene regulation of macrophage M1 and M2 polarization to bridge TF regulatory networks and immune disease genetic variants, (2) define the regulatory landscape of primary T helper cell subsets and (3) dissect the effect of perturbing lineage TFs via arrayed CRISPR screens in spontaneously differentiating human induced pluripotent stem cells. SUM-seq offers a cost-effective, scalable solution for ultra-high-throughput single-cell multiomic sequencing, accelerating the unraveling of complex gene regulatory networks in cell differentiation, responses to perturbations and disease studies.

DOI: 10.1038/s41592-025-02700-8

Source: https://www.nature.com/articles/s41592-025-02700-8