苏黎世联邦理工学院Randall J. Platt和瑞士伯尔尼大学Andrew J. Macpherson研究组合作的研究开发了利用前哨细胞转录记录对肠道功能进行无创性评估的方法。2022年5月13日出版的《科学》杂志发表了这项成果。

研究人员展示了使用条形码CRISPR阵列的多路记录，从而能够在体内重建同基因菌株的转录记忆。因此，Record-seq提供了一个可扩展的非侵入性平台，用于在整个肠道中探究肠道和微生物生理学，而无需对宿主生理学进行改变，并且可以确定单个微生物遗传差异如何改变微生物适应宿主肠道环境的方式。

据介绍，通过从RNA中获取CRISPR间隔子进行转录记录，使工程大肠杆菌具有合成记忆，该记录是通过Record-seq揭示转录组规模实现的。穿过胃肠道的微生物哨兵捕获了与宿主相互作用的广泛基因和途径，包括由于宿主饮食改变、诱导炎症和微生物组复杂性导致的分子环境数量变化。

附：英文原文

Title: Noninvasive assessment of gut function using transcriptional recording sentinel cells

Author: Florian Schmidt, Jakob Zimmermann, Tanmay Tanna, Rick Farouni, Tyrrell Conway, Andrew J. Macpherson, Randall J. Platt

Issue&Volume: 2022-05-13

Abstract: Transcriptional recording by CRISPR spacer acquisition from RNA endows engineered Escherichia coli with synthetic memory, which through Record-seq reveals transcriptome-scale records. Microbial sentinels that traverse the gastrointestinal tract capture a wide range of genes and pathways that describe interactions with the host, including quantitative shifts in the molecular environment that result from alterations in the host diet, induced inflammation, and microbiome complexity. We demonstrate multiplexed recording using barcoded CRISPR arrays, enabling the reconstruction of transcriptional histories of isogenic bacterial strains in vivo. Record-seq therefore provides a scalable, noninvasive platform for interrogating intestinal and microbial physiology throughout the length of the intestine without manipulations to host physiology and can determine how single microbial genetic differences alter the way in which the microbe adapts to the host intestinal environment.

DOI: abm6038

Source: https://www.science.org/doi/10.1126/science.abm6038