Dissecting the initiation of female meiosis in the mouse at single-cell resolution

Abstract

Germ cell meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, in mammals, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By comparing the signature gene expression pattern of 4 meiotic germ cell clusters, we found that the 4 cell clusters correspond to different cell status en route to meiosis progression, and therefore, our research here characterized detailed transcriptome dynamics during meiotic prophase I. Reconstructing the progression of meiosis along pseudotime, we identified several new genes and molecular pathways with potential critical roles in the mitosis/meiosis transition and early meiotic progression. Last, the heterogeneity within somatic cell populations was also discussed and different cellular states were identified. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving meiosis initiation and progression in female germ cells and ovarian somatic cells.

TAF4b transcription networks regulating early oocyte differentiation

“…A similar analysis from a second scRNA-seq dataset of whole ovaries from earlier E11.5 to E14.5 time points supported these findings (Ge et al 2021) (Fig S1).…”

Single-cell transcriptome landscape of ovarian cells during primordial follicle assembly in mice

“…Another is regard to the incorporate of biological replicates [77,78]. Although the biological replicates are suggested to eliminate batch effects, it seems the 1 replicate is still more popular in the single-cell dataset of recent publications [47,61]. In the present study, the application of 1 replicate may be considered as a potential limitation; however, the canonical knowledge in the field of PF formation, as well as the experimental verification, makes us confident for our results.…”

“…Through using this method, we revealed several TFs at distinct stages, such as Nr3c1, Foxo1, Brca1, Kdm5a, and Kdm5b at the germ cell nest stage; Smarcb1, Hes1, Stat3, and Sox15 during the period of PF assembly; and Foxo3 mainly limited postnatal period (Fig 5). It is worth noting that Nr3c1 has been revealed as the meiotic specific TF in oocyte; furthermore, Brca1, Kdm5a, and Kdm5b have previously been detected in meiotic oocyte [61]. Meanwhile, recent studies have shown that FOXO3 plays a critical role in the maintenance of PF dormancy and Foxo3 knockout lead to follicles overactivation [62][63][64], and the results indicate Foxo3 is a suppressor of PF activation and may be required for their formation.…”

Insights from the Applications of Single-Cell Transcriptomic Analysis in Germ Cell Development and Reproductive Medicine

“…One study subjected the cell populations in female mouse gonads to scRNA-seq to elucidate the molecular mechanism underlying female germ cell development [63]. The genital ridges of the E11.5 mouse embryo and the ovaries of the E12.5, E13.5, and E14.5 mouse embryos were analyzed.…”