Single‐cell RNA sequencing reveals the landscape of early female germ cell development

Abstract

Meiosis initiation is a crucial step for the production of haploid gametes, which occurs from anterior to posterior in fetal ovaries. The asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations, which limits the studies of meiosis initiation and progression at a higher resolution level. To dissect the process of meiosis initiation, we investigated the transcriptional profiles of 19 363 single germ cells collected from E12.5, E14.5, and E16.5 mouse fetal ovaries. Clustering analysis identified seven groups and defined dozens of corresponding transcription factors, providing a global view of cellular differentiation from primordial germ cells toward meiocytes. Furthermore, we explored the dynamics of gene expression within the developmental trajectory with special focus on the critical state of meiosis. We found that meiosis initiation occurs as early as E12.5 and the cluster of oogonia_4 is the critical state between mitosis and meiosis. Our data provide key insights into the transcriptome features of peri‐meiotic female germ cells, which offers new information not only on meiosis initiation and progression but also on screening pathogenic mutations in meiosis‐associated diseases.

Transcriptome Profiling of the Ovarian Cells at the Single-Cell Resolution in Adult Asian Seabass

“…The scRNA-seq analysis has been widely applied to studying the germ cells or gonadal development in organisms in recent years. However, up to now, most investigations on ovarian transcriptome focus mainly on limited species, including human (Liu et al, 2009;Zhang et al, 2018), monkey (Wang et al, 2020), mouse (Dean, 2002;Zhao et al, 2020), zebrafish (Zhu et al, 2018), and fly (Slaidina et al, 2020), which revealed the remarkable interspecies variations and conservations during ovarian development across phyla.…”

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

“…The expression of TFs associated with meiosis initiation, including Msx1, Msx2, Cdx2, Sox4, Gata2, and Bmyc, was markedly upregulated at the pre-leptotene stage of PGCs. Meanwhile, Dmrtc2 and Taf4b expression was upregulated in the late meiotic stage, whereas Taf9b expression was upregulated at the late meiotic stage of PGCs [50]. The expression of pluripotent genes, Nanog and Oct4, and their associated genes, Dppa2 and Dppa4, was downregulated in PGCs at E11.5 [51].…”

Establishing and maintaining fertility: the importance of cell cycle arrest

“…These subtle transcriptional changes cannot be detected using traditional global RNA sequencing methods. However, recent single-cell sequencing approaches have been successfully used to uncover other discreet spatial and temporal regulators of meiosis (Niu and Spradling 2020;Zhao et al 2020). Both studies performed fine-scale analyses of the germ cell meiotic transcriptomes covering the E12.5 and E14.5 (Niu and Spradling 2020) and E12.5, E14.5, and E16.5 (Zhao et al 2020) time points, respectively.…”

“…However, recent single-cell sequencing approaches have been successfully used to uncover other discreet spatial and temporal regulators of meiosis (Niu and Spradling 2020;Zhao et al 2020). Both studies performed fine-scale analyses of the germ cell meiotic transcriptomes covering the E12.5 and E14.5 (Niu and Spradling 2020) and E12.5, E14.5, and E16.5 (Zhao et al 2020) time points, respectively. Another unreviewed preprint also analyzed germ cell transcriptomes between E10.5 and E16.5 (Mayère et al 2021).…”

“…Together with the information obtained about the initiation of meiosis, these data sets have also provided a wealth of information about Cip/Kip family expression between E12.5 and E16.5 in mice (Niu and Spradling 2020;Zhao et al 2020). Both studies showed that Cdkn1a expression peaks in the preleptotene stage of germ cell development and decreases as the germ cells enter the leptotene stage of meiosis (Niu and Spradling 2020;Zhao et al 2020). In contrast, Cdkn1c expression peaks at the leptotene stage, before decreasing as the germ cells continue through meiosis (Niu and Spradling 2020).…”