Tree Shrews Mirror Human Sperm Development Better Than Mice, Study Finds

Tree shrews may serve as a better laboratory stand-in for human sperm production than the mouse, according to a cross-species single-cell study published in Nature Communications. Researchers led by Hui-Juan Lin, Wei-Bo Kang and Lan-Ping Xie integrated histology with single-nucleus RNA sequencing data from human, rhesus macaque, mouse and tree shrew testes to evaluate how faithfully each animal’s spermatogenic cells mirror the human transcriptional landscape.

The motivation lies in evolutionary biology: spermatogenesis evolves rapidly, and some genes involved in human sperm development are absent or divergent in mice, limiting the mouse’s utility as a model. Primate models such as macaques are closer to humans biologically but face practical and ethical constraints in laboratory research. Tree shrews, small mammals closely related to primates, are easy to keep and breed in laboratory settings, making them an attractive candidate for comparison.

The analysis showed that transcriptional landscapes in tree shrew spermatogenic cells, particularly late-stage spermatids, more closely resemble those of primates than of mice. Conservation and enrichment analyses identified two core gene modules shared among humans, macaques and tree shrews but distinct in mice, suggesting a primate-like genetic program of sperm cell development that the tree shrew retains.

Gene expression trajectories across the stages of sperm development also aligned between tree shrew and primates, including for genes that lack murine orthologs. This means that even genes with no mouse counterpart follow a similar developmental expression pattern in tree shrews and primates. Immunostaining and RNA-FISH experiments supported the representative expression patterns observed in the sequencing data.

The authors note that these findings define contexts in which tree shrews can complement existing models of human spermatogenesis and male infertility research. The study is an open-access article published on 29 October 2026 and shared early as a citable, peer-reviewed accepted version subject to further edits before the final Version of Record.

Subject of Research: Cross-species single-cell transcriptomic comparison of testis gene expression in humans, macaques, mice and tree shrews

Article Title: Tree shrew more closely recapitulates primate spermatogenesis than the mouse in cross-species single-cell transcriptomic analyses

Article References: Lin, H.-J., Kang, W.-B., Xie, L.-P., Hu, S., Li, Y., Bi, R., Yao, Y.-G., & Zheng, P. (2026). Tree shrew more closely recapitulates primate spermatogenesis than the mouse in cross-species single-cell transcriptomic analyses. Nature Communications. https://doi.org/10.1038/s41467-026-77781-w

Image Credits: AI Generated

DOI: 10.1038/s41467-026-77781-w

Keywords: spermatogenesis, tree shrew, single-nucleus RNA sequencing, testis, primate model, male infertility, transcriptomics, comparative genomics, rhesus macaque, mouse model, Tree, shrew