In a groundbreaking advance for primate biology and cellular genomics, researchers have unveiled a comprehensive molecular atlas of cell types from the gray mouse lemur, Microcebus murinus, providing unprecedented insights into the deep molecular relationships across diverse tissues and organs. Employing cutting-edge transcriptomic profiling and sophisticated dimensionality reduction techniques, the study reconstructed a layered landscape of cellular identities and unexpectedly illuminated cross-tissue molecular convergences that challenge classical tissue compartment boundaries.
Central to this monumental effort was the condensation of transcriptomic data into pseudo-bulk expression profiles for each molecularly defined cell type, enabling a high-resolution yet tractable view of cell-type similarities across the entire lemur body. By summarizing mean gene expression values from thousands of individual cells per type, the researchers applied uniform manifold approximation and projection (UMAP) to distill complex high-dimensional data into visually interpretable, two-dimensional embeddings. This innovative approach revealed overarching global patterns while enabling the detection of subtle, biologically meaningful relationships among seemingly unrelated cell types.
Strikingly, the data demonstrated that cell types within the same tissue compartments invariably clustered together, underlining the preserved gene expression signatures that define organ-specific cellular roles. For instance, endothelial cells formed a remarkably coherent compartment across diverse organs, emphasizing the evolutionary conservation of their molecular programs. Similarly, neural compartment cells, encompassing both central nervous system glial cells and neurons, clustered closely—a finding that intriguingly hints at shared molecular foundations despite functional differences.
Yet, the true scientific intrigue arose from the identification of cross-compartmental molecular convergences that defy traditional histological classifications. Perhaps the most astonishing was the pronounced molecular similarity between male germ cells—specifically spermatogonia—and immune progenitor cells, which in the molecular atlas, appeared more closely allied to each other than to other progenitor or proliferating cells from their respective tissue milieus. This unexpected convergence was not an isolated phenomenon within mouse lemurs; parallel patterns were observed in human and mouse comparative datasets, suggesting a conserved evolutionary signature among these progenitors.
Delving deeper into these similarities, the study highlighted the shared expression of pivotal cell cycle regulators, including M phase-specific genes such as CCNB1 and VRK1, underscoring the aligned mitotic machinery that governs proliferation in these distinct progenitor populations. Beyond cell cycle genes, non-cell-cycle factors like TESMIN and RSPH14 were selectively expressed in both spermatogonia and immune progenitors—genes implicated in the maintenance and regulation of stemness, potentially revealing a shared ancestral program modulating progenitor cell identity and function across biological systems.
Further expanding on cross-compartment parallels, the researchers uncovered that peripheral nervous system glial cells, namely myelinating and non-myelinating Schwann cells, molecularly segregated with stromal cells rather than their central glial counterparts, such as oligodendrocytes. Differential gene expression analyses pinpointed a cohort of extracellular matrix components and remodeling genes—including COL3A1, LAMC1, and SOCS3—that were enriched in both Schwann and stromal cells but conspicuously absent from central glia and neurons. This molecular signature suggests a specialized role for peripheral glia functioning in concert with local stromal environments to regulate extracellular matrix dynamics and tissue architecture.
While the global organization of cell types adhered largely to compartmental demarcations, epithelial cells stood out as an exception, exhibiting pronounced tissue-specific molecular signatures that overshadowed broader compartment-level clustering. Basal and suprabasal epithelial subtypes in skin, for instance, formed discrete clusters distinctly separate from corresponding cell types in the tongue epithelium despite analogous physiological roles. This tissue-specific stratification underscores the nuanced molecular adaptations underpinning epithelial function in diverse organ systems.
Intriguingly, the atlas also revealed a peculiar cluster comprising a unique epithelial population from the lung tissue of a single lemur individual, which, upon further investigation, was identified as metastatic uterine endometrial cancer cells—highlighting the atlas’s sensitivity to pathological conditions and its potential utility for translational oncology studies in primate models.
Moreover, the comprehensive pairwise correlation matrix of all cell-type pseudo-bulk profiles, encompassing approximately 750 by 750 comparisons, provided a quantifiable framework to discern degrees of molecular relatedness. This robust analytical matrix not only reinforced the compartmental distinctions but also spotlighted remarkable outliers, facilitating hypothesis generation about lineage relationships, cellular plasticity, and functional convergence.
Comparative analyses with human and mouse datasets underscored the evolutionary conservation of these molecular relationships, lending credibility to the lemur atlas as an informative model for primate biology and human disease. The consistency of certain cross-compartmental similarities—such as the spermatogonia-immune progenitor convergence—across species suggests fundamental regulatory pathways orchestrating stem cell behavior and proliferative control.
Taken together, this vast molecular atlas of the mouse lemur delineates a cellular taxonomy that transcends conventional tissue boundaries, revealing both expected and surprising molecular compatriotries. These findings open new avenues for understanding stem cell biology, intercellular communication, and tissue homeostasis in primates, with far-reaching implications for regenerative medicine and evolutionary biology.
The mouse lemur’s emerging status as a model organism is bolstered by this atlas, which serves as a rich resource for probing cellular heterogeneity, lineage relationships, and disease susceptibility in a primate context closely related to humans. As such, the atlas promises to catalyze innovative research across neuroscience, immunology, developmental biology, and oncology.
Ultimately, by combining state-of-the-art transcriptomic profiling with meticulous bioinformatic integration and comparative cross-species analyses, this work sets a new standard for comprehensive molecular cell atlases. It underscores the transformative power of single-cell technologies to redefine our understanding of cellular identity, revealing the molecular tapestries that knit together the primate body’s diverse cell populations.
Subject of Research: Molecular cell atlas and transcriptomic relationships across tissues in the gray mouse lemur (Microcebus murinus), focusing on cell-type molecular convergence and divergence.
Article Title: A molecular cell atlas of mouse lemur, an emerging model primate.
Article References:
The Tabula Microcebus Consortium., Ezran, C., Liu, S. et al. A molecular cell atlas of mouse lemur, an emerging model primate. Nature (2025). https://doi.org/10.1038/s41586-025-09113-9
Image Credits: AI Generated
