ArticleFrontiers in cell and developmental biology2026
Unveiling novel insights into gene expression in monkey testes through single-nucleus-based analysis.
Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Spermatogenesis is a highly intricate and tightly regulated process that involves the coordinated interplay of various cell types. Understanding the expression profiles of individual cells is crucial for unraveling the intricacies of spermatogenesis. This study aimed to uncover novel gene expression patterns and regulatory features during primate spermatogenesis. Methods: We performed single-nucleus RNA sequencing on testicular tissues from cynomolgus macaques at four developmental stages (infancy, puberty, adulthood, and aged). To explore chromatin regulatory landscapes, we also conducted single-nucleus ATAC sequencing on pubertal testes. We integrated both datasets and applied clustering, differential expression analysis, gene ontology enrichment, pseudo time trajectory reconstruction, and transcription factor motif enrichment to characterize cell types, differentiation trajectories, and cell-type-specific regulatory programs. Results: Our integrated analysis comprehensively characterized all major germ and somatic cell types, including a previously unrecognized quiescent undifferentiated spermatogonial (uSPG) subtype in early spermatogenesis that exhibits a transcriptomic state distinct from canonical type A spermatogonial stem cells, which we provisionally term as uSPG1. We also revealed the differentiation states, and expression and function of genes within distinct cell types during spermatogenesis. Notably, we found that classic niche factors essential for spermatogonial stem cell maintenance, including Conclusion: These findings offer a refined single-nucleus-resolution view of primate spermatogenesis, revealing a novel undifferentiated germ cell state and emphasizing the need for further exploration of Sertoli cells in male reproductive biology. Our results underscore the power of combined single-nucleus RNA and ATAC sequencing for investigating complex reproductive tissues. This research enhances our understanding of the intricate mechanisms governing spermatogenesis and may offer new perspectives on male fertility regulation.
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