A molecular cell atlas of mouse lemur, an emerging model primate

Camille Ezran, Shixuan Liu, Stephen Chang, Jingsi Ming, Olga Botvinnik, Lolita Penland, Alexander Tarashansky, Antoine Morree, Kyle J. Travaglini, Jia Zhao, Gefei Wang, Kazuteru Hasegawa, Hosu Sin, Rene Sit, Jennifer Okamoto, Rahul Sinha, Yue Zhang, Caitlin J. Karanewsky, Jozeph L. Pendleton, Maurizio Morri, Martine Perret, Fabienne Aujard, Lubert Stryer, Steven Artandi, Margaret T. Fuller, Irving L. Weissman, Thomas A. Rando, James E. Ferrell, Bo Wang, Iwijn Vlaminck, Can Yang, Kerriann M. Casey, Megan A. Albertelli, Angela Oliveira Pisco, Jim Karkanias, Norma Neff, Angela Ruohao Wu, Stephen R. Quake () and Mark A. Krasnow ()
Additional contact information
Camille Ezran: Stanford University School of Medicine
Shixuan Liu: Stanford University School of Medicine
Stephen Chang: Stanford University School of Medicine
Jingsi Ming: East China Normal University
Olga Botvinnik: Chan Zuckerberg Biohub
Lolita Penland: Chan Zuckerberg Biohub
Alexander Tarashansky: Chan Zuckerberg Biohub
Antoine Morree: Stanford University School of Medicine
Kyle J. Travaglini: Stanford University School of Medicine
Jia Zhao: Hong Kong University of Science and Technology
Gefei Wang: Hong Kong University of Science and Technology
Kazuteru Hasegawa: Stanford University School of Medicine
Hosu Sin: Stanford University School of Medicine
Rene Sit: Chan Zuckerberg Biohub
Jennifer Okamoto: Chan Zuckerberg Biohub
Rahul Sinha: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
Yue Zhang: Howard Hughes Medical Institute, Stanford University School of Medicine
Caitlin J. Karanewsky: Stanford University School of Medicine
Jozeph L. Pendleton: Stanford University School of Medicine
Maurizio Morri: Chan Zuckerberg Biohub
Martine Perret: National Museum of Natural History
Fabienne Aujard: National Museum of Natural History
Lubert Stryer: Stanford University School of Medicine
Steven Artandi: Stanford University School of Medicine
Margaret T. Fuller: Stanford University School of Medicine
Irving L. Weissman: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
Thomas A. Rando: Stanford University School of Medicine
James E. Ferrell: Stanford University School of Medicine
Bo Wang: Stanford University
Iwijn Vlaminck: Cornell University
Can Yang: Hong Kong University of Science and Technology
Kerriann M. Casey: Stanford University School of Medicine
Megan A. Albertelli: Stanford University School of Medicine
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Jim Karkanias: Chan Zuckerberg Biohub
Norma Neff: Chan Zuckerberg Biohub
Angela Ruohao Wu: Hong Kong University of Science and Technology
Stephen R. Quake: Chan Zuckerberg Biohub
Mark A. Krasnow: Stanford University School of Medicine

Nature, 2025, vol. 644, issue 8075, 173-184

Abstract: Abstract 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 mouse1. The atlas provides a cellular and molecular foundation for studying this model primate and establishes a general approach for characterizing other emerging model organisms.

Date: 2025
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DOI: 10.1038/s41586-025-09113-9

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