School of Biological Science, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
J Transl Med. 2023 Nov 27;21(1):859. doi: 10.1186/s12967-023-04722-2.
The testis is a complex organ that undergoes extensive developmental changes from the embryonic stage to adulthood. The development of germ cells, which give rise to spermatozoa, is tightly regulated by the surrounding somatic cells.
To better understand the dynamics of these changes, we constructed a transcriptional cell atlas of the testis, integrating single-cell RNA sequencing data from over 26,000 cells across five developmental stages: fetal germ cells, infants, childhood, peri-puberty, and adults. We employed various analytical techniques, including clustering, cell type assignments, identification of differentially expressed genes, pseudotime analysis, weighted gene co-expression network analysis, and evaluation of paracrine cell-cell communication, to comprehensively analyze this transcriptional cell atlas of the testis.
Our analysis revealed remarkable heterogeneity in both somatic and germ cell populations, with the highest diversity observed in Sertoli and Myoid somatic cells, as well as in spermatogonia, spermatocyte, and spermatid germ cells. We also identified key somatic cell genes, including RPL39, RPL10, RPL13A, FTH1, RPS2, and RPL18A, which were highly influential in the weighted gene co-expression network of the testis transcriptional cell atlas and have been previously implicated in male infertility. Additionally, our analysis of paracrine cell-cell communication supported specific ligand-receptor interactions involved in neuroactive, cAMP, and estrogen signaling pathways, which support the crucial role of somatic cells in regulating germ cell development.
Overall, our transcriptional atlas provides a comprehensive view of the cell-to-cell heterogeneity in the testis and identifies key somatic cell genes and pathways that play a central role in male fertility across developmental stages.
睾丸是一个复杂的器官，从胚胎期到成年期经历了广泛的发育变化。生殖细胞的发育，产生精子，受到周围体细胞的严格调控。
为了更好地了解这些变化的动态，我们构建了睾丸转录细胞图谱，整合了来自五个发育阶段的超过 26000 个细胞的单细胞 RNA 测序数据：胎儿生殖细胞、婴儿、儿童、青春期前和成人。我们采用了各种分析技术，包括聚类、细胞类型分配、差异表达基因鉴定、伪时间分析、加权基因共表达网络分析以及旁分泌细胞-细胞通讯的评估，全面分析了睾丸转录细胞图谱。
我们的分析揭示了体细胞和生殖细胞群体中的显著异质性，在 Sertoli 和 Myoid 体细胞以及精原细胞、精母细胞和精子细胞中观察到最大的多样性。我们还鉴定了关键的体细胞基因，包括 RPL39、RPL10、RPL13A、FTH1、RPS2 和 RPL18A，它们在睾丸转录细胞图谱的加权基因共表达网络中具有高度影响力，并且之前与男性不育有关。此外，我们对旁分泌细胞-细胞通讯的分析支持了神经活性、cAMP 和雌激素信号通路中涉及的特定配体-受体相互作用，这些作用支持体细胞在调节生殖细胞发育中的关键作用。
总体而言，我们的转录图谱提供了睾丸细胞间异质性的全面视图，并确定了关键的体细胞基因和通路，它们在发育阶段对男性生育力起着核心作用。
