Depicting the dynamic transcriptional and epigenetic landscape of testis development in pubertal Simmental cattle
- J Anim Sci Biotechnol. 2026 May 18;17(1):96. doi: 10.1186/s40104-026-01406-x.
- 1. State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
- 2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- 3. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- 4. State Key Laboratory of Animal Biotech Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China.
- 5. College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
- 6. State Key Laboratory of Animal Biotech Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China. [email protected].
- 7. National Germplasm Center of Domestic Animal Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. [email protected].
- 8. State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. [email protected].
- # Contributed equally.
Background: The reproductive development of Simmental cattle, a vital breed for global beef production, remains poorly understood at the molecular and cellular levels. A systematic analysis of the regulatory mechanisms governing germ cell fate transitions during testicular development is essential for advancing breeding efficiency and reproductive technologies in cattle.
Results: Using integrated single-cell RNA Sequencing (scRNA-seq) and single-nucleus ATAC Sequencing (sNucATAC-seq) on testicular tissues from Simmental cattle across postnatal (PN), prepubertal (PP), and pubertal (PUB) stages, we identified core transcriptional regulators-including E2F1, BCLAF1, and YY1-that govern germ cell fate transitions. Several signaling pathways, such as TGF-β, MAPK, ErbB, and AMPK, were found to participate in spermatogenic processes. Sertoli cells were classified into three functional subtypes: Stage 1 is associated with the transition from spermatogonial stem cells (SSCs) to differentiating spermatogonia (Diff-SPG), Stage 2 correlates with development from Diff-SPG to spermatocytes (SPC), and Stage 3 coincides with the transformation from SPC to spermatids (SPT). Cross-species comparative transcriptomics with humans, pigs, and mice revealed conserved pathways in germ cell development, with E2F1 notably conserved during the SSC-to-Diff-SPG transition.
Conclusions: This study deciphers the regulatory network controlling germ cell fate transitions during bovine testicular development. The identification of conserved regulators and pathways provides novel insights into spermatogenesis and supports the development of strategies to overcome meiotic barriers in stem cell systems. These findings pave the way for precision breeding and advanced reproductive technologies in mammals.