New cell atlas reveals biological secrets of the mouse lemur – and its close link to human health

Scientists routinely cure mice of Alzheimer’s disease, cancer, diabetes, and more. The same cannot be said for humans, and that’s because of a biological gap: Despite the fact that humans and mice are mammals that share 92% of their DNA, there are fundamental differences between human and mouse cells, and the activities that occur in those cells. 

Researchers, therefore, need alternative species to study that better represent human genetics and human traits. Now, a team of more than 150 experts, led by scientists at the Chan Zuckerberg Biohub San Francisco and Stanford University, unveil a cell atlas for a unique non-human primate — the fluffy mouse lemur. 

In two Nature papers, published on July 30, 2025, the researchers present Tabula Microcebus — named for the Latin genus of mouse lemurs, the world’s smallest and fastest-reproducing primates — and demonstrate how the atlas can be used to characterize mouse lemur genes, physiology, and disease. Using single-cell RNA sequencing, the Tabula Microcebus team profiled 226,000 cells from 27 mouse lemur organs and tissues. 

Using that data, the team discovered thousands of previously unidentified mouse lemur genes, including more than 400 primate genes present in mouse lemurs but absent in mice; defined 750 mouse lemur cell types and their full gene expression profiles; systematically explored and mapped the lemur immune and endocrine systems; and identified genes implicated in health conditions humans share with lemurs, such as obesity, cataracts, osteoarthritis, Alzheimer’s disease, and more.

The atlas, and its potential uses, are highlighted in an accompanying Nature commentary. 

“Now we have the cellular and molecular foundation to begin exploring some of the most significant and interesting features of human biology shared among primates,” says Mark Krasnow, the Paul and Mildred Berg Professor and professor of biochemistry at Stanford, also a Howard Hughes Medical Institute Investigator and co-leader of the project. 

“This new atlas helps us see what genes and cell types are unique to primates and different from other mammals, like the mouse,” says co-leader Stephen Quake, Chief Scientific Advisor of the Chan Zuckerberg Initiative and the Lee Otterson Professor of Bioengineering and professor of applied physics at Stanford. “We’re going to learn a lot about health and evolution from this atlas, and it is also serving as a powerful training set for the AI Virtual Cell Models we are building.”

Building infrastructure for impact

The new cell atlas is the latest in a string of ambitious “Tabula” projects completed by scientists at the San Francisco Biohub and collaborators. To date, the team has created or spearheaded cell atlases for the mouse (Tabula Muris); aging mice (Tabula Muris Senis); the fruit fly (the Fly Cell Atlas); and humans (Tabula Sapiens). A valuable companion to genomic data, each atlas maps hundreds of cell types in each of these organisms and shows how differences in gene expression give rise to these cell types.

The human data, as well as data for mouse, aging mouse, fruit fly, and now mouse lemur, are publicly available, either through an open-access, user-friendly tool called Chan Zuckerberg CELL by GENE (CZ CELLxGENE), developed by CZI’s Science Technology team, or other free online repositories.

The Tabula atlases have been built by collaborative teams of tissue experts, pathologists, cell and molecular biologists, and computational biologists. The collaborators developed methods to rapidly gather, share, and analyze fresh tissue samples from dozens of organs from a single donor in parallel, then process those samples as soon as possible using single-cell transcriptomics and advanced computational analysis of the sequencing data. “We originally developed the infrastructure as part of a big team-science project to do the mouse atlas,” says Quake. “It was serendipitous to then use the same infrastructure for the mouse lemur.”

Tabula Microcebus became a reality thanks to Krasnow — a lung specialist who served as one of the tissue experts for Tabula Muris — who has studied mouse lemur genetics for more than 10 years. Mouse lemurs have many appealing qualities for a model organism: a nocturnal primate native to Madagascar, mouse lemurs are small (about twice the size of a mouse), develop and mature quickly, are abundant in the wild, and are easy to care for in laboratory settings. Yet little was known about their genetics or cellular and molecular biology, so when Krasnow became aware of four aged laboratory mouse lemurs from France that veterinarians were planning to euthanize for humane reasons, he reached out to Quake, who was then co-president of the San Francisco Biohub. 

“I asked Steve whether we could apply the same technologies from Tabula Muris to a non-human primate,” recalls Krasnow. “If so, in one collaborative effort, we could go from knowing almost nothing about the cells, genes, and gene expression patterns of this species to having knowledge at a level comparable to mice and humans, two of the best-studied animals in the world.”

Quake mobilized the team and the effort began. As with prior atlases, the team followed specific protocols to procure multiple organs from each donor and process them in parallel within a day. Next came months of sequencing by the San Francisco Biohub’s Genomics Platform, and then data analysis and annotation across the collaborating groups, with many teams working together to identify, name, and then characterize cell types and their corresponding gene expression patterns. 

Annotating that much data was no small feat, but it was worth the effort, says Angela Pisco, a lead data scientist on the project. “The Tabula projects speak to the Biohub’s vision of advancing risky research that requires a large team committed to an end goal of delivering a dataset that a whole community can take advantage of,” says Pisco, who was associate director of bioinformatics at the San Francisco Biohub and is now director of computational biology at Insitro.

Once the atlas was assembled, the Tabula Microcebus team put it to work characterizing mouse lemur genes, mutations, physiology, and disease. A large part of the analysis involved comparing mouse, mouse lemur, and human cell types and gene expression profiles to identify what was common to all three species or unique to each one. “It’s the first time we’ve really been able to articulate and discover which cell types are found only in one of these species,” says Quake. 

Data from the mouse lemur atlas is being used to train and test CZI’s latest biological AI model, TranscriptFormer, a generative, multi-species model for single-cell transcriptomics. The data has also been used in a dozen other papers revealing aspects of mouse lemur biology and disease, and in the development of new single-cell analysis technologies. 

The atlas was made possible by an international collaborative effort involving the San Francisco Biohub; numerous groups at Stanford; the CNRS-MNHN (Muséum National d’Histoire Naturelle in Brunoy, France); and teams at HKUST, Cornell, A*STAR (Agency for Science, Technology and Research in Singapore), as well as UC San Francisco and other institutions.

The Chan Zuckerberg Initiative provided significant funding for the Tabula Microcebus work. Other funders of the project include Howard Hughes Medical Institute, the Vera Moulton Wall Center for Pulmonary Vascular Disease at Stanford, and the University of Hong Kong.