A complete Sigmodon hispidus genome and dynamic single-cell transcriptomics reveal evolutionarily conserved responses to RSV infection

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-09-17 DOI:10.1126/scitranslmed.adw7535

Shijie Qin, Xiao Qu, Chao Lv, Yali Hou, Xiaoyan Li, Fei Ma, Shuguang Tan, Kefang Liu, Ye Yin, Yi Jing, Xuancheng Lu, Xin Zhao, Xiaopeng Ma, George Fu Gao

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引用次数: 0

Abstract

The cotton rat (Sigmodon hispidus) has emerged as a preclinical model for human respiratory syncytial virus (RSV) research because of its ability to support effective viral replication and recapitulate disease; however, the mechanisms supporting this evolutionarily conserved phenotype remain unclear. Here, we report both the chromosomal genome and respiratory single-cell transcriptomic atlas of the cotton rat throughout the course of RSV infection. Phylogenetic analysis showed that cotton rats are in different evolutionary branches from common mouse and rat models and exhibit substantial conservation of tissue profiles with humans. The respiratory cell atlas, alveolar cell trajectory, and distribution of potential viral receptors are also similar to those of humans, explaining the superiority of cotton rats as an RSV infection model. The target cells of RSV, including club cells, secretory2 cells, mesothelial cells, and nerve-associated astrocytes, were expanded after infection. We also identified differential transcriptional regulators, specific antiviral proteins, and cytokines that could be translated into potential clinical markers in humans. Candidate host factors were also identified, which will enable the exploration of host-RSV interactions and offer a source of therapeutic targets.

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一个完整的Sigmodon hispidus基因组和动态单细胞转录组揭示了进化上对RSV感染的保守反应

棉鼠（Sigmodon hispidus）已成为人类呼吸道合胞病毒（RSV）研究的临床前模型，因为它能够支持有效的病毒复制和概括疾病；然而，支持这种进化保守表型的机制仍不清楚。在此，我们报告了棉鼠在整个RSV感染过程中的染色体基因组和呼吸单细胞转录组图谱。系统发育分析表明，棉花大鼠与普通小鼠和大鼠模型处于不同的进化分支，并表现出与人类相当的组织特征守恒。呼吸道细胞图谱、肺泡细胞轨迹和潜在病毒受体的分布也与人类相似，说明棉花大鼠作为RSV感染模型的优越性。RSV的靶细胞包括俱乐部细胞、分泌细胞、间皮细胞和神经相关星形胶质细胞，感染后扩增。我们还发现了可以转化为人类潜在临床标志物的差异转录调节因子、特异性抗病毒蛋白和细胞因子。候选宿主因子也被确定，这将有助于探索宿主- rsv相互作用，并提供治疗靶点的来源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.