Tabula Microcebus: A transcriptomic cell atlas of mouse lemur, an emerging primate model organism

Abstract

Mouse lemurs are the smallest, fastest reproducing, and among the most abundant primates, and an emerging model organism for primate biology, behavior, health and conservation. Although much has been learned about their physiology and their Madagascar ecology and phylogeny, little is known about their cellular and molecular biology. Here we used droplet- and plate-based single cell RNA-sequencing to profile 226,000 cells from 27 mouse lemur organs and tissues opportunistically procured from four donors clinically and histologically characterized. Using computational cell clustering, integration, and expert cell annotation, we defined and biologically organized over 750 mouse lemur molecular cell types and their full gene expression profiles. These include cognates of most classical human cell types, including stem and progenitor cells, and the developmental programs for spermatogenesis, hematopoiesis, and other adult tissues. We also described dozens of previously unidentified or sparsely characterized cell types and subtypes. We globally compared cell type expression profiles to define the molecular relationships of cell types across the body, and explored primate cell type evolution by comparing mouse lemur cell profiles to those of the homologous cells in human and mouse. This revealed cell type specific patterns of primate cell specialization even within a single tissue compartment, as well as many cell types for which lemur provides a better human model than mouse. The atlas provides a cellular and molecular foundation for studying this primate model organism, and establishes a general approach for other emerging model organisms.

Organism-wide mapping of MHC class I and II expression in mouse lemur cells and tissues

“…The epithelial cells of the kidney nephron form a continuum in overall gene expression that resembles their spatial gradients 14 (data present for L2, L3, L4) (Fig. 5).…”

“…The heat maps show the expression levels of the MHC genes in cells that had been placed on a trajectory 14 . In all plots the direction of the trajectory is shown by arrows and the major cell type in each trajectory is indicated.…”

“…We used the pseudo-time developmental trajectory, described in The Tabula Microcebus Consortium, et al 14 , to assess differences in MHC expression in the myeloid and erythroid cells of bone and bone marrow (Fig. 4).…”

“…The copyright holder for this preprint this version posted March 2, 2022. ; https://doi.org/10.1101/2022.02.28.482372 doi: bioRxiv preprint detectable cell-surface expression [31][32][33][34][35][36] . The trajectory described for the sperm cells of L4 followed their developmental pathway starting from spermatogonia and maturing into late spermatids 14 . Mapping MHC expression on this trajectory showed that although the levels of expression were much lower than seen for other cell compartments, specific patterns of expression could be discerned.…”

“…To do this, we developed bioinformatic methods that determine MHC class I and II expression levels from 10x droplet-based scRNAseq data. These methods were applied to the Tabula Microcebus cell atlas (https://tabula-microcebus.ds.czbiohub.org/about) 14 , which comprises single cell transcriptomes from 27 organs and tissues of four individual mouse lemurs ( Microcebus murinus ). We analyzed 215,524 cells, representing 267 cell annotations and 739 molecular cell types.…”