Ezran Camille, Liu Shixuan, Chang Stephen, Ming Jingsi, Botvinnik Olga, Penland Lolita, Tarashansky Alexander, de Morree Antoine, Travaglini Kyle J, Zhao Jia, Wang Gefei, Hasegawa Kazuteru, Sin Hosu, Sit Rene, Okamoto Jennifer, Sinha Rahul, Zhang Yue, Karanewsky Caitlin J, Pendleton Jozeph L, Morri Maurizio, Perret Martine, Aujard Fabienne, Stryer Lubert, Artandi Steven, Fuller Margaret T, Weissman Irving L, Rando Thomas A, Ferrell James E, Wang Bo, De Vlaminck Iwijn, Yang Can, Casey Kerriann M, Albertelli Megan A, Pisco Angela Oliveira, Karkanias Jim, Neff Norma, Wu Angela Ruohao, Quake Stephen R, Krasnow Mark A
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
Nature. 2025 Aug;644(8075):173-184. doi: 10.1038/s41586-025-09113-9. Epub 2025 Jul 30.
Mouse lemurs are the smallest and fastest reproducing primates, as well as one of the most abundant, and they are emerging as a model organism for primate biology, behaviour, health and conservation. Although much has been learnt about their ecology and phylogeny in Madagascar and their physiology, little is known about their cellular and molecular biology. Here we used droplet-based and plate-based single-cell RNA sequencing to create Tabula Microcebus, a transcriptomic atlas of 226,000 cells from 27 mouse lemur organs opportunistically obtained from four donors clinically and histologically characterized. Using computational cell clustering, integration and expert cell annotation, we define and biologically organize more than 750 lemur molecular cell types and their full gene expression profiles. This includes cognates of most classical human cell types, including stem and progenitor cells, and differentiating cells along the developmental trajectories of spermatogenesis, haematopoiesis and other adult tissues. We also describe dozens of previously unidentified or sparsely characterized cell types. We globally compare expression profiles to define the molecular relationships of cell types across the body, and explore primate cell and gene expression evolution by comparing lemur transcriptomes to those of human, mouse and macaque. This reveals cell-type-specific patterns of primate specialization and many cell types and genes for which the mouse lemur provides a better human model than mouse. The atlas provides a cellular and molecular foundation for studying this model primate and establishes a general approach for characterizing other emerging model organisms.
鼠狐猴是最小且繁殖速度最快的灵长类动物，也是数量最多的灵长类动物之一，正逐渐成为灵长类生物学、行为学、健康和保护研究的模式生物。尽管人们已经对它们在马达加斯加的生态、系统发育以及生理学有了很多了解，但对它们的细胞和分子生物学却知之甚少。在此，我们使用基于液滴和基于平板的单细胞RNA测序技术创建了鼠狐猴细胞图谱（Tabula Microcebus），这是一个来自27个鼠狐猴器官的226,000个细胞的转录组图谱，这些器官是从四名捐赠者那里通过临床和组织学特征鉴定后 opportunistically 获取的。通过计算细胞聚类、整合和专家细胞注释，我们定义并从生物学角度组织了750多种狐猴分子细胞类型及其完整的基因表达谱。这包括大多数经典人类细胞类型的同源物，包括干细胞和祖细胞，以及沿着精子发生、造血和其他成年组织发育轨迹分化的细胞。我们还描述了数十种以前未被识别或特征描述较少的细胞类型。我们在全球范围内比较表达谱以定义身体各细胞类型之间的分子关系，并通过将狐猴转录组与人类、小鼠和猕猴的转录组进行比较来探索灵长类细胞和基因表达的进化。这揭示了灵长类特化的细胞类型特异性模式以及许多细胞类型和基因，对于这些细胞类型和基因，鼠狐猴比小鼠更适合作为人类模型。该图谱为研究这种模式灵长类动物提供了细胞和分子基础，并建立了一种表征其他新兴模式生物的通用方法。
