Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin 300052, China.
Cells. 2022 Jan 20;11(3):332. doi: 10.3390/cells11030332.
The fate of fetal germ cells (FGCs) in primordial follicles is largely determined by how they interact with the surrounding granulosa cells. However, the molecular mechanisms underlying this interactive process remain poorly understood. Here, we develop a computational model to characterize how individual genes program and rewire cellular crosstalk across FGCs and somas, how gene regulatory networks mediate signaling pathways that functionally link these two cell types, and how different FGCs diversify and evolve through cooperation and competition during embryo development. We analyze single-cell RNA-seq data of human female embryos using the new model, identifying previously uncharacterized mechanisms behind follicle development. The majority of genes (70%) promote FGC-soma synergism, only with a small portion (4%) that incur antagonism; hub genes function reciprocally between the FGC network and soma network; and germ cells tend to cooperate between different stages of development but compete in the same stage within a developmental embryo. Our network model could serve as a powerful tool to unravel the genomic signatures that mediate folliculogenesis from single-cell omics data.
原始卵泡中胎儿生殖细胞 (FGC) 的命运在很大程度上取决于它们与周围颗粒细胞的相互作用方式。然而，这种相互作用过程的分子机制仍知之甚少。在这里，我们开发了一个计算模型来描述个体基因如何对 FGC 和体细胞之间的细胞串扰进行编程和重新布线，基因调控网络如何介导功能连接这两种细胞类型的信号通路，以及不同的 FGC 如何在胚胎发育过程中通过合作和竞争进行多样化和进化。我们使用新模型分析了人类女性胚胎的单细胞 RNA-seq 数据，鉴定了卵泡发育背后以前未被描述的机制。大多数基因 (70%) 促进 FGC-体细胞协同作用，只有一小部分 (4%) 产生拮抗作用；枢纽基因在 FGC 网络和体细胞网络之间相互作用；生殖细胞在不同发育阶段倾向于合作，但在发育胚胎的同一阶段竞争。我们的网络模型可以作为一种强大的工具，从单细胞组学数据中揭示介导卵泡发生的基因组特征。
