4.6 Article

A Single-Cell Omics Network Model of Cell Crosstalk during the Formation of Primordial Follicles

Journal

CELLS
Volume 11, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/cells11030332

Keywords

primordial follicle; evolutionary game theory; fetal germ cell-soma interaction; gene regulatory network modeling; niche index

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Funding

  1. NNSFC [7192072]
  2. NSF [CMMI-1932991]

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In this study, a computational model was developed to investigate the molecular mechanisms underlying the interaction between fetal germ cells and surrounding granulosa cells. By analyzing single-cell RNA-seq data of human embryos, previously unknown mechanisms of follicle development were identified.
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.

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