PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：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。
方法：为了更好地了解这些变化的动态，我们构建了睾丸的转录细胞图谱，整合来自五个发育阶段的26,000多个细胞的单细胞RNA测序数据：胎儿生殖细胞，婴儿,童年,青春期周围,和成年人。我们采用了各种分析技术，包括聚类，单元格类型分配,差异表达基因的鉴定，伪时间分析，加权基因共表达网络分析，以及旁分泌细胞间通讯的评估，全面分析睾丸的转录细胞图谱。
结果：我们的分析揭示了体细胞和生殖细胞群体的显著异质性，在Sertoli和Myoid体细胞中观察到最高的多样性，以及精原细胞，精母细胞,和精子细胞。我们还确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很高的影响力，并且以前与男性不育有关。此外,我们对旁分泌细胞-细胞通讯的分析支持与神经活性有关的特异性配体-受体相互作用，cAMP,和雌激素信号通路，这支持了体细胞在调节生殖细胞发育中的关键作用。
结论：总体而言，我们的转录图谱提供了睾丸中细胞间异质性的全面视图,并确定了关键的体细胞基因和途径,这些基因和途径在跨发育阶段的男性生育力中起着核心作用.
方法：为了更好地了解这些变化的动态，我们构建了睾丸的转录细胞图谱，整合来自五个发育阶段的26,000多个细胞的单细胞RNA测序数据：胎儿生殖细胞，婴儿,童年,青春期周围,和成年人。我们采用了各种分析技术，包括聚类，单元格类型分配,差异表达基因的鉴定，伪时间分析，加权基因共表达网络分析，以及旁分泌细胞间通讯的评估，全面分析睾丸的转录细胞图谱。
结果：我们的分析揭示了体细胞和生殖细胞群体的显著异质性，在Sertoli和Myoid体细胞中观察到最高的多样性，以及精原细胞，精母细胞,和精子细胞。我们还确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很高的影响力，并且以前与男性不育有关。此外,我们对旁分泌细胞-细胞通讯的分析支持与神经活性有关的特异性配体-受体相互作用，cAMP,和雌激素信号通路，这支持了体细胞在调节生殖细胞发育中的关键作用。
结论：总体而言，我们的转录图谱提供了睾丸中细胞间异质性的全面视图,并确定了关键的体细胞基因和途径,这些基因和途径在跨发育阶段的男性生育力中起着核心作用.
