斯坦福大学医学院Mark A. Krasnow小组的研究开发出了鼠狐猴细胞图谱揭示了灵长类动物的基因、生理和疾病。该项研究成果发表在2025年7月30日出版的《自然》上。

在一篇论文中，该课题组研究人员对母狐猴的27个器官进行了大规模单细胞RNA测序。课题组研究人员鉴定了超过750种分子细胞类型，表征了它们的转录组谱，并为灵长类动物细胞类型的进化提供了见解。

在这里，该研究组将生成的图谱用于描述母狐猴的基因、生理、疾病和突变。研究组发现了以前未被识别的狐猴基因和数百个新的剪接连接，包括小鼠中缺失的超过85000个灵长类剪接连接。课题组研究人员通过比较健康和疾病中关键免疫基因的全球表达谱，以及绘制免疫细胞的发育、运输和激活图谱，系统地探索狐猴的免疫系统。

该研究团队描述了灵长类特异性和狐猴特异性的生理和疾病，包括免疫程序的分子特征，狐猴脂肪细胞和转移性子宫内膜癌，类似于人类恶性肿瘤。该研究团队在小鼠中缺失了400多种灵长类基因的表达模式，其中许多与人类的表达模式相似，有些与人类疾病有关。最后，该团队通过鉴定小鼠中缺失的三种灵长类免疫基因中自然发生的无义突变并分析其转录表型，为反向遗传分析提供了一个实验框架。这项工作为母猴的分子和遗传分析奠定了基础，并为未来的研究优先考虑灵长类动物的基因、同工型、生理和疾病。

研究人员表示，母狐猴（狐猴科）是一种新兴的灵长类模式生物，但它们的遗传学、细胞和分子生物学在很大程度上仍未被探索。

附：英文原文

Title: Mouse lemur cell atlas informs primate genes, physiology and disease

Author: Ezran, Camille, Liu, Shixuan, Chang, Stephen, Ming, Jingsi, Guethlein, Lisbeth A., Wang, Michael F. Z., Dehghannasiri, Roozbeh, Olivieri, Julia, Frank, Hannah K., Tarashansky, Alexander, Koh, Winston, Jing, Qiuyu, Botvinnik, Olga, Antony, Jane, Pisco, Angela Oliveira, Karkanias, Jim, Yang, Can, Ferrell, James E., Boyd, Scott D., Parham, Peter, Long, Jonathan Z., Wang, Bo, Salzman, Julia, De Vlaminck, Iwijn, Wu, Angela Ruohao, Quake, Stephen R., Krasnow, Mark A.

Issue&Volume: 2025-07-30

Abstract: Mouse lemurs (Microcebus spp.) are an emerging primate model organism, but their genetics, cellular and molecular biology remain largely unexplored. In an accompanying paper1, we performed large-scale single-cell RNA sequencing of 27 organs from mouse lemurs. We identified more than 750 molecular cell types, characterized their transcriptomic profiles and provided insight into primate evolution of cell types. Here we use the generated atlas to characterize mouse lemur genes, physiology, disease and mutations. We uncover thousands of previously unidentified lemur genes and hundreds of thousands of new splice junctions including over 85,000 primate splice junctions missing in mice. We systematically explore the lemur immune system by comparing global expression profiles of key immune genes in health and disease, and by mapping immune cell development, trafficking and activation. We characterize primate-specific and lemur-specific physiology and disease, including molecular features of the immune program, lemur adipocytes and metastatic endometrial cancer that resembles the human malignancy. We present expression patterns of more than 400 primate genes missing in mice, many with similar expression patterns to humans and some implicated in human disease. Finally, we provide an experimental framework for reverse genetic analysis by identifying naturally occurring nonsense mutations in three primate immune genes missing in mice and by analysing their transcriptional phenotypes. This work establishes a foundation for molecular and genetic analyses of mouse lemurs and prioritizes primate genes, isoforms, physiology and disease for future study.

DOI: 10.1038/s41586-025-09114-8

Source: https://www.nature.com/articles/s41586-025-09114-8