Mouse lemur cell atlas informs primate genes, physiology and disease

Camille Ezran, Shixuan Liu, Stephen Chang, Jingsi Ming, Lisbeth A. Guethlein, Michael F. Z. Wang, Roozbeh Dehghannasiri, Julia Olivieri, Hannah K. Frank, Alexander Tarashansky, Winston Koh, Qiuyu Jing, Olga Botvinnik, Jane Antony, Angela Oliveira Pisco, Jim Karkanias, Can Yang, James E. Ferrell, Scott D. Boyd, Peter Parham, Jonathan Z. Long, Bo Wang, Julia Salzman, Iwijn Vlaminck, 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
Lisbeth A. Guethlein: Stanford University School of Medicine
Michael F. Z. Wang: Cornell University
Roozbeh Dehghannasiri: Stanford University School of Medicine
Julia Olivieri: Stanford University School of Medicine
Hannah K. Frank: Stanford University School of Medicine
Alexander Tarashansky: Stanford University
Winston Koh: Agency of Science Technology and Research
Qiuyu Jing: Hong Kong University of Science and Technology
Olga Botvinnik: Chan Zuckerberg Biohub
Jane Antony: Stanford University School of Medicine
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Jim Karkanias: Chan Zuckerberg Biohub
Can Yang: Hong Kong University of Science and Technology
James E. Ferrell: Stanford University School of Medicine
Scott D. Boyd: Stanford University School of Medicine
Peter Parham: Stanford University School of Medicine
Jonathan Z. Long: Stanford University School of Medicine
Bo Wang: Stanford University
Julia Salzman: Stanford University School of Medicine
Iwijn Vlaminck: Cornell University
Angela Ruohao Wu: Hong Kong University of Science and Technology
Stephen R. Quake: Stanford University
Mark A. Krasnow: Stanford University School of Medicine

Nature, 2025, vol. 644, issue 8075, 185-196

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41586-025-09114-8

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