Establishing and maintaining fertility: the importance of cell cycle arrest

Frost, Emily R; Taylor, Güneş; Baker, Mark A.; Lovell‐Badge, Robin; Sutherland, Jessie M.

doi:10.1101/gad.348151.120

Cited by 15 publications

(12 citation statements)

References 142 publications

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“…The cysts are broken down to form primordial follicles where somatic pregranulosa cells surround oocytes. 6 The oocytes within the primordial follicles are subsequently arrested at the diplotene stage of meiotic prophase I until the oocytes restart meiosis in puberty. 7,8 Reserve of dormant oocytes within primordial follicles of ovarian cortex determines mammalian female fecundity.…”

Section: Introductionmentioning

confidence: 99%

“…The oogonia undergo several cycles of mitotic division with incomplete cytokinesis forming germ cell nests or cysts. The cysts are broken down to form primordial follicles where somatic pregranulosa cells surround oocytes 6 . The oocytes within the primordial follicles are subsequently arrested at the diplotene stage of meiotic prophase I until the oocytes restart meiosis in puberty 7,8 .…”

Section: Introductionmentioning

confidence: 99%

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A single‐cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex

et al. 2022

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The ovary as one of the most dynamic organs produces steroids to orchestrate female secondary sexual characteristics, harbors ovarian reserve for oocytes, releases mature oocytes for fertilization, and maintains pregnancy. Yak (Bos grunniens) is the only bovid animal that can adapt to the harsh climatic conditions on the Qinghai‐Tibetan Plateau (altitudes of over 3000 m above sea level). However, the cellular atlas is composed of oocytes and other somatic cells, and their individual molecular characteristics remain to be elucidated in the yak ovary. Here, single‐cell RNA sequencing (scRNA‐seq) was performed to delineate the molecular signature of various cell types in the yak ovarian cortex. A cellular atlas of yak ovarian cortex was constructed successfully on the basis of the differentially expressed genes (DEGs) from the distinct cell types and their functional enrichment analysis, comprising endothelial cells, nature kill cells, stromal cells, smooth muscle cells, oocytes, macrophages, epithelial cells, and granulosa cells. Meanwhile, the signature genes were determined based on their expression specificity in each cell type. A cell‐to‐cell communication network was built in light of the differentially overexpressed ligand and receptor genes from each cell type. Further, the oocytes were subdivided into four subtypes based on their individual DEGs and the functional enrichment of the DEGs. FST and TOP2A were identified as maker genes for oocytes by immunostaining in the yak ovarian cortex. The cellular atlas reveals the biological characteristics of the ovarian cortex at the cellular molecular level and provides insights into female reproductive biology via cellular communications in the yak.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A single‐cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex

et al. 2022

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“…Immunostaining for SSEA1 and integrin β3, two surface markers for PGCLCs (Hayashi et al ., 2011), revealed 4.3% and 6.0% double positive cells in BVSC-ESC and GFP-ESC derived EBs, further confirming the induction of PGC cell fate. Oogenesis requires interactive signals between oocytes and the surrounding gonadal somatic cells, which results in the formation of follicles (Frost et al, 2021; O’Connell and Pepling, 2021). IVD mimics in vivo development, by aggregating PGCLCs with somatic cells isolated from E12.5 female gonads in low-binding plates.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Aizawa

Ozonov

Kawamura

et al. 2023

Preprint

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Germ cells are the origin of new individuals. Hence, specifying germ cell identity is crucial for reproduction. The recent establishment of in vitro culture systems for generating oocytes from mouse pluripotent stem cells provides a basis for progress in studies of oogenesis and reproductive technology. However, currently the developmental competence of in vitro generated oocytes is low compared to in vivo grown oocytes. The causes underlying poor oocyte quality remain to be determined. By reconstituting germ cell development in culture from different developmental starting points within gametogenesis, we show that the differentiation of primordial germ cells (PGCs) and primordial germ cell-like cells (PGCLCs) to growing oocytes (GROs), as well as the subsequent growth of follicles are critical culture steps for specifying competence of fully-grown oocytes (FGOs) for preimplantation development. A systematic comparison of transcriptomes of single oocytes having undergone different in vitro culture trajectories identifies genes normally upregulated during oocyte growth to be susceptible for mis-regulation during in vitro oogenesis. Many of such genes have been described as targets of Polycomb repressive complexes (PRCs). Deregulation of Polycomb repression therefore likely perturbs the accumulation of cytoplasmic factors and/or setting of chromatin states in FGOs that are required for embryonic development after fertilization. Conversely, in vitro derived oocytes often displayed failure of zygotic genome activation (ZGA) and abnormal acquisition of 5-hydroxymethylcytosine (5hmC) on maternal chromosomes after activation. In addition, subcellular delocalization of pyruvate dehydrogenase (PDH) and of STELLA were observed suggesting new molecular markers for defective oocyte development. Our study identifies epigenetic regulation at an early stage of oogenesis as crucial for developmental competence and suggests specific in vitro culture steps as targets for improving oocyte quality.

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“…As the only somatic cell type in the niche that has direct contact with germ cells, Sertoli cells can produce a variety of growth factors that are necessary for the development of male germ cells during spermatogenesis (Zheng et al, 2022). Importantly, the advent of new sequencing technologies, such as single-cell RNA sequencing (scRNA-seq), has promoted the identification of the key genes controlling testicular cell development (Frost et al, 2021). Currently, the elucidation of gene expression dynamics during the development of male germ cells and Sertoli cells using single-cell transcriptomics has been reported in mice (Hermann et al, 2018;Tan and Wilkinson, 2020).…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomics reveals male germ cells and Sertoli cells developmental patterns in dairy goats

Ren

Hao

Qiao

et al. 2022

Front. Cell Dev. Biol.

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Spermatogenesis holds considerable promise for human-assisted reproduction and livestock breeding based on stem cells. It occurs in seminiferous tubules within the testis, which mainly comprise male germ cells and Sertoli cells. While the developmental progression of male germ cells and Sertoli cells has been widely reported in mice, much less is known in other large animal species, including dairy goats. In this study, we present the data of single cell RNA sequencing (scRNA-seq) for 25,373 cells from 45 (pre-puberty), 90 (puberty), and 180-day-old (post-puberty) dairy goat testes. We aimed to identify genes that are associated with key developmental events in male germ cells and Sertoli cells. We examined the development of spermatogenic cells and seminiferous tubules from 15, 30, 45, 60, 75, 90, 180, and 240-day-old buck goat testes. scRNA-seq clustering analysis of testicular cells from pre-puberty, puberty, and post-puberty goat testes revealed several cell types, including cell populations with characteristics of spermatogonia, early spermatocytes, spermatocytes, spermatids, Sertoli cells, Leydig cells, macrophages, and endothelial cells. We mapped the timeline for male germ cells development from spermatogonia to spermatids and identified gene signatures that define spermatogenic cell populations, such as AMH, SOHLH1, INHA, and ACTA2. Importantly, using immunofluorescence staining for different marker proteins (UCHL1, C-KIT, VASA, SOX9, AMH, and PCNA), we explored the proliferative activity and development of male germ cells and Sertoli cells. Moreover, we identified the expression patterns of potential key genes associated with the niche-related key pathways in male germ cells of dairy goats, including testosterone, retinoic acid, PDGF, FGF, and WNT pathways. In summary, our study systematically investigated the elaborate male germ cells and Sertoli cells developmental patterns in dairy goats that have so far remained largely unknown. This information represents a valuable resource for the establishment of goat male reproductive stem cells lines, induction of germ cell differentiation in vitro, and the exploration of sequential cell fate transition for spermatogenesis and testicular development at single-cell resolution.

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Establishing and maintaining fertility: the importance of cell cycle arrest

Cited by 15 publications

References 142 publications

A single‐cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex

A single‐cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex

Comprehensive comparison of female germ cell developmentin vitroandin vivoidentifies epigenetic gene regulation crucial for oocyte development and embryonic competence

Single-cell transcriptomics reveals male germ cells and Sertoli cells developmental patterns in dairy goats

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