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

Ge, Wei; Wang, Junjie; Zhang, Ruiqian; Tan, Shao-Jing; Zhang, Fa‐Li; Liu, Wen-Xiang; Li, Lan; Sun, Xiao‐Feng; Cheng, Shun‐Feng; Dyce, Paul W.; Felici, Massimo De; Shen, Wei

doi:10.1101/803668

Cited by 4 publications

(5 citation statements)

References 75 publications

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“…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).…”

Section: Taf4b Expression Peaks At E165 In Female Embryonic Germ Cellssupporting

confidence: 70%

TAF4b transcription networks regulating early oocyte differentiation

Gura

Relovska

Abt

et al. 2021

Preprint

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Establishment of a healthy ovarian reserve is contingent upon numerous regulatory pathways during embryogenesis. Previously, mice lacking TBP-associated factor 4b (Taf4b) were shown to exhibit a diminished ovarian reserve. However, potential oocyte-intrinsic functions of TAF4b have not been examined. Here we use a combination of gene expression profiling and chromatin mapping to characterize the TAF4b gene regulatory network in mouse oocytes. We find that Taf4b-deficient oocytes display inappropriate expression of meiotic, chromatin, and X-linked genes, and unexpectedly we found a connection with Turner Syndrome pathways. Using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), we observed TAF4b enrichment at genes involved in meiosis and DNA repair, some of which are differentially expressed in Taf4b-deficient oocytes. Interestingly, TAF4b target genes were enriched for Sp/KLF family motifs rather than TATA-box, suggesting an alternate mode of promoter interaction. Together, our data connects several gene regulatory nodes that contribute to the ovarian reserve.

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“…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).…”

Section: Taf4b Expression Peaks At E165 In Female Embryonic Germ Cellssupporting

confidence: 70%

TAF4b transcription networks regulating early oocyte differentiation

Gura

Relovska

Abt

et al. 2021

Preprint

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“…Great progress has been made since single-cell transcriptomics has been applied to studies of the female reproductive system 43 , 45 , 49 , 50 . Specifically, the transcriptome landscape of the whole process of folliculogenesis in humans has been described, and single-cell transcriptomic analyses of monkey ovaries have identified ovarian aging associated dysregulation of antioxidative pathways 54 .…”

Section: Discussionmentioning

confidence: 99%

“…The development of single-cell transcriptomics has revolutionized the dissection of cellular heterogeneity and cell fate transition 36 - 38 . From such studies, many novel insights have been proposed regarding reproductive system development, derived from single cell datasets in both males 39 - 42 and females 43 - 46 . Recently, the credo of a limited ovarian reserve has been reinforced by single-cell analysis of human ovarian cortical tissue, where no oogonial stem cells were detected 47 .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the credo of a limited ovarian reserve has been reinforced by single-cell analysis of human ovarian cortical tissue, where no oogonial stem cells were detected 47 . In addition, the transcriptomic landscapes of germ cells during early murine oogenesis have been delineated, which concentrates on two vital germline events, meiotic initiation 43 , 48 and PF assembly 49 . Furthermore, the respective waves of PF formation in the ovarian cortex and medulla disclose two distinct pathways for pre-granulosa cell differentiation 50 .…”

Section: Introductionmentioning

confidence: 99%

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Single-cell transcriptome dissection of the toxic impact of Di (2-ethylhexyl) phthalate on primordial follicle assembly

Wang¹,

Tian²,

Li³

et al. 2021

Theranostics

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Rationale: Accumulated evidence indicates that environmental plasticizers are a threat to human and animal fertility. Di (2-ethylhexyl) phthalate (DEHP), a plasticizer to which humans are exposed daily, can trigger reproductive toxicity by acting as an endocrine-disrupting chemical. In mammals, the female primordial follicle pool forms the lifetime available ovarian reserve, which does not undergo regeneration once it is established during the fetal and neonatal period. It is therefore critical to examine the toxicity of DEHP regarding the establishment of the ovarian reserve as it has not been well investigated. Methods: The ovarian cells of postnatal pups, following maternal DEHP exposure, were prepared for single cell-RNA sequencing, and the effects of DEHP on primordial follicle formation were revealed using gene differential expression analysis and single-cell developmental trajectory. In addition, further biochemical experiments, including immunohistochemical staining, apoptosis detection, and Western blotting, were performed to verify the dataset results. Results: Using single-cell RNA sequencing, we revealed the gene expression dynamics of female germ cells and granulosa cells following exposure to DEHP in mice. Regarding germ cells: DEHP impeded the progression of follicle assembly and interfered with their developmental status, while key genes such as Lhx8 , Figla, and others, strongly evidenced the reduction. As for granulosa cells: DEHP likely inhibited their proliferative activity, and activated the regulation of cell death. Furthermore, the interaction between ovarian cells mediated by transforming growth factor-beta signaling, was disrupted by DEHP exposure, since the expression of GDF9, BMPR1A, and SMAD3 was affected. In addition, DNA damage and apoptosis were elevated in germ cells and/or somatic cells. Conclusion: These findings offer substantial novel insights into the reproductive toxicity of DEHP exposure during murine germ cell cyst breakdown and primordial follicle formation. These results may enhance the understanding of DEHP exposure on reproductive health.

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“…The advent of scRNA-seq technology has enabled the detection of changes in transcriptome expression in specific types of ovarian cells, determination of a cell development map, and establishment of the network of interactions between different cells. Currently, scRNA-seq has been used to construct a developmental map of mouse ovarian germ cells during meiotic entry and PF assembly 35 , 36 . In addition, Wang et al used scRNA-seq to compare single-cell transcriptional differences between non-human primates' young ovaries and aged ovaries, providing evidence for a molecular mechanism of human ovarian aging 36 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

et al. 2021

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Rationale: Zearalenone (ZEN), a pollutant in our daily diet, seriously threatens the reproductive health of humans and animals. The primordial follicle (PF) assembly in the mouse occurs during the perinatal period, which determines the whole ovarian reserve in reproductive lifespan. In the current investigation, we administered ZEN orally to perinatal mice from 16.5 days post coitum (dpc) to postnatal day 3 (PD3), and single-cell RNA sequencing (scRNA-seq) was performed on PD0 and PD3 ovarian tissues in the offspring to check ZEN toxic to primordial follicle formation at the single cell level. Methods: Ovarian tissues ( in vivo ) were examined by single cell RNA sequencing analysis, Immunostaining, and Western blotting. Ovarian tissues ( in vitro ) were examined by qRT-PCR, Immunostaining, and Western blotting. Results: We found that ZEN exposure altered the developmental trajectory of both germ cells and granulosa cells. Furthermore, after establishing the cell-cell communication network between germ cells and granulosa cells, we found that this was perturbed by ZEN exposure, especially during the Hippo signaling pathway. Conclusions: This study showed that ZEN affected the status of germ cells and granulosa cells through the Hippo signaling pathway and blocked the assembly of PFs. This research contributes to our deeper understanding of the mechanisms of toxicity in different cell types and the disruption of normal intercellular signaling by ZEN exposure.

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

Cited by 4 publications

References 75 publications

TAF4b transcription networks regulating early oocyte differentiation

TAF4b transcription networks regulating early oocyte differentiation

Single-cell transcriptome dissection of the toxic impact of Di (2-ethylhexyl) phthalate on primordial follicle assembly

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

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