Kavli Affiliate: Angela Wu
| Authors: The Tabula Microcebus Consortium, Camille Ezran, Shixuan Liu, 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, Stephen Chang, Angela Oliveira Pisco, Jim Karkanias, Can Yang, James E. Ferrell, Jr., Scott D. Boyd, Peter Parham, Jonathan Z. Long, Bo Wang, Julia Salzman, Iwijn De Vlaminck, Angela Wu, Stephen R. Quake and Mark A. Krasnow
| Summary:
Abstract Mouse lemurs (Microcebus spp.) are an emerging model organism for primate biology, behavior, health, and conservation. Although little has been known about their cellular and molecular biology, in the accompanying paper we used large-scale single cell RNA-sequencing of 27 organs and tissues to identify over 750 molecular cell types and their full transcriptomic profiles. Here we use this extensive transcriptomic dataset to uncover thousands of previously unidentified genes and hundreds of thousands of new splice junctions in the reference genome that globally define lemur gene structures and cell-type selective expression and splicing and to investigate gene expression evolution. We use the atlas to explore the biology and function of the lemur immune system, including the expression profiles across the organism of all MHC genes and chemokines in health and disease, and the mapping of neutrophil and macrophage development, trafficking, and activation, their local and global responses to infection, and primate-specific aspects of the program. We characterize other examples of primate-specific physiology and disease such as unique features of lemur adipocytes that may underlie their dramatic seasonal rhythms, and spontaneous metastatic endometrial cancer that models the human gynecological malignancy. We identify and describe the organism-wide expression profiles of over 400 primate genes missing in mice, some implicated in human disease. Thus, an organism-wide molecular cell atlas and molecular cell autopsies can enhance gene discovery, structure definition, and annotation in a new model organism, and can identify and elucidate primate-specific genes, physiology, diseases, and evolution. Competing Interest Statement The authors have declared no competing interest.