摄动-多模态:一个在完整哺乳动物组织中进行成像和测序的汇集基因筛选的平台

IF 42.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Cell Pub Date : 2025-06-12 DOI:10.1016/j.cell.2025.05.022
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
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引用次数: 0

摘要

后生动物的生命需要在空间组织的细胞类型中数千个基因的协调活动。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。在这里,我们提出了Perturb-Multimodal (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,我们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,我们测量了对相同扰动的全转录组反应。我们应用Perturb-Multi来研究小鼠肝脏中的数百种遗传扰动。我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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

Perturb-Multimodal: A platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue
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.
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来源期刊
Cell
Cell 生物-生化与分子生物学
CiteScore
110.00
自引率
0.80%
发文量
396
审稿时长
2 months
期刊介绍: Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.
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