Chakravorty Arun, Simons Benjamin D, Yoshida Shosei, Cai Long
California Institute of Technology, Department of Biology and Biological Engineering, Pasadena, CA 91106.
UCLA-Caltech Medical Scientist Training Program, Los Angeles, CA 90095.
bioRxiv. 2024 Nov 4:2024.10.28.620681. doi: 10.1101/2024.10.28.620681.
Spermatogenesis is characterized by the seminiferous epithelial cycle, a periodic pattern of germ cell differentiation with a wave-like progression along the length of seminiferous tubules. While key signaling and metabolic components of the cycle are known, the transcriptional changes across the cycle and the correlations between germ cell and somatic lineages remain undefined. Here, we use spatial transcriptomics via RNA SeqFISH+ to profile 2,638 genes in 216,090 cells in mouse testis and identify a periodic transcriptional pattern across tubules that precisely recapitulates the seminiferous epithelial cycle, enabling us to map cells to specific timepoints along the developmental cycle. Analyzing gene expression in somatic cells reveals that Sertoli cells exhibit a cyclic transcriptional profile closely synchronized with germ cell development while other somatic cells do not demonstrate such synchronization. Remarkably, in mouse testis with drug-induced ablation of germ cells, Sertoli cells independently maintain their cyclic transcriptional dynamics. By analyzing expression data, we identify an innate retinoic acid cycle, a network of transcription factors with cyclic activation, and signaling from germ cells that could interact with this network. Together, this work leverages spatial geometries for mapping the temporal dynamics and reveals a regulatory mechanism in spermatogenesis where Sertoli cells oscillate and coordinate with the cyclical progression of germ cell development.
精子发生的特征是生精上皮周期，这是一种生殖细胞分化的周期性模式，沿着生精小管的长度呈波浪状进展。虽然已知该周期的关键信号和代谢成分，但整个周期的转录变化以及生殖细胞和体细胞谱系之间的相关性仍不明确。在这里，我们通过RNA SeqFISH+使用空间转录组学对小鼠睾丸中216,090个细胞中的2,638个基因进行分析，并确定了整个小管的周期性转录模式，该模式精确地概括了生精上皮周期，使我们能够将细胞映射到发育周期中的特定时间点。对体细胞中基因表达的分析表明，支持细胞表现出与生殖细胞发育紧密同步的周期性转录谱，而其他体细胞则没有表现出这种同步性。值得注意的是，在药物诱导生殖细胞消融的小鼠睾丸中，支持细胞独立维持其周期性转录动态。通过分析表达数据，我们确定了一个内在的视黄酸循环、一个具有周期性激活的转录因子网络，以及来自生殖细胞的可能与该网络相互作用的信号。总之，这项工作利用空间几何学来绘制时间动态图谱，并揭示了精子发生中的一种调节机制，即支持细胞与生殖细胞发育的周期性进展同步振荡并协调。
