2025年6月12日，霍华德休斯医学院庄小威研究组在《细胞》杂志发表论文，宣布他们开发出Perturb Multimodal：一个在完整哺乳动物组织中进行成像和测序的混合遗传筛查平台。

该团队提出了摄动-多模态（Perturb-Multi），这是一种配对成像和测序方法，用于在混合遗传扰动的组织中构建大规模的多模态基因型-表型图谱。利用成像技术，该课题组研究人员识别单个细胞的扰动，同时测量它们的基因表达谱和亚细胞形态。使用单细胞测序，该课题组测量了对相同扰动的全转录组反应。该课题组研究人员应用Perturb-Multi来研究肝脏中数百种遗传扰动。他们的数据提示了肝细胞分区、未折叠蛋白反应和脂肪变性动态控制的遗传调控因子和机制。Perturb-Multi加速发现复杂细胞和组织生理学的遗传基础，并为新兴的细胞功能机器学习模型提供关键的训练数据。

研究人员表示，后生动物的生命需要在空间组织的细胞类型中协调各种基因的活动。要了解组织功能的基础，需要对体内不同细胞和组织表型的遗传控制进行剖析。

附：英文原文

Title: Perturb-Multimodal: A platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue

Author: Reuben A. Saunders, William E. Allen, Xingjie Pan, Jaspreet Sandhu, Jiaqi Lu, Thomas K. Lau, Karina Smolyar, Zuri A. Sullivan, Catherine Dulac, Jonathan S. Weissman, Xiaowei Zhuang

Issue&Volume: 2025-06-12

Abstract: Metazoan life requires the coordinated activities of thousands of genes in spatially organized cell types. Understanding the basis of tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes in vivo. Here, we present Perturb-Multimodal (Perturb-Multi), a paired imaging and sequencing method to construct large-scale, multimodal genotype-phenotype maps in tissues with pooled genetic perturbations. Using imaging, we identify perturbations in individual cells while simultaneously measuring their gene expression profiles and subcellular morphology. Using single-cell sequencing, we measure full transcriptomic responses to the same perturbations. We apply Perturb-Multi to study hundreds of genetic perturbations in the mouse liver. Our data suggest the genetic regulators and mechanisms underlying the dynamic control of hepatocyte zonation, the unfolded protein response, and steatosis. Perturb-Multi accelerates discoveries of the genetic basis of complex cell and tissue physiology and provides critical training data for emerging machine learning models of cellular function.

DOI: 10.1016/j.cell.2025.05.022

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00572-0