耶路撒冷的希伯来大学Nathalie Q. Balaban课题组的一项最新研究探明了利用Microcolony-seq揭示单细胞的表型遗传。2025年8月26日出版的《细胞》发表了这项成果。

利用Microcolony-seq（一种通过分析源自单个细菌细胞的微菌落来捕获遗传异质性的方法），该课题组研究人员揭示了细菌维持宿主环境长期遗传的泛素能力。值得注意的是，该团队观察到生长到静止阶段消除了表观遗传。通过利用每个微群体的这种记忆，Microcolony -seq将大量RNA测序（RNA-seq）与全基因组测序和表型分析相结合，以检测不同的亚群体及其适应度优势。将这种方法直接应用于受感染的人类样本，使他们能够发现丰富多样的遗传表型。他们的观察表明，细菌记忆可能在革兰氏阴性菌和革兰氏阳性菌中都是一种普遍现象。Microcolony-seq为合理设计治疗方法提供了潜在的靶标，并具有同时靶向共存亚群的能力。

据介绍，揭示表型异质性是理解发育和应激反应等过程的基础。由于单个细菌的mRNA丰度较低，确定生物学相关的异质性仍然是一个挑战。

附：英文原文

Title: Uncovering phenotypic inheritance from single cells with Microcolony-seq

Author: Raya Faigenbaum-Romm, Noam Yedidi, Orit Gefen, Naama Katsowich-Nagar, Lior Aroeti, Irine Ronin, Maskit Bar-Meir, Ilan Rosenshine, Nathalie Q. Balaban

Issue&Volume: 2025-08-26

Abstract: Uncovering phenotypic heterogeneity is fundamental to understanding processes such as development and stress responses. Due to the low mRNA abundance in single bacteria, determining biologically relevant heterogeneity remains a challenge. Using Microcolony-seq, a methodology that captures inherited heterogeneity by analyzing microcolonies originating from single bacterial cells, we uncover the ubiquitous ability of bacteria to maintain long-term inheritance of the host environment. Notably, we observe that growth to stationary phase erases the epigenetic inheritance. By leveraging this memory within each microcolony, Microcolony-seq combines bulk RNA sequencing (RNA-seq) with whole-genome sequencing and phenotypic assays to detect the distinct subpopulations and their fitness advantages. Applying this directly to infected human samples enables us to uncover a wealth of diverse inherited phenotypes. Our observations suggest that bacterial memory may be a widespread phenomenon in both Gram-negative and Gram-positive bacteria. Microcolony-seq provides potential targets for the rational design of therapies with the power to simultaneously target the coexisting subpopulations.

DOI: 10.1016/j.cell.2025.08.001

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00915-8