Stem Cells in Mammalian Gonads

Wu, Ji; Ding, Xinbao; Wang, Jian

doi:10.1007/978-3-319-31973-5_11

Cited by 6 publications

(4 citation statements)

References 100 publications

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“…The development of FGSCs plays an important role in the maintenance of ovarian function. Although a few studies have revealed the molecular mechanisms of proliferation, differentiation, and apoptosis in FGSCs [8,9,10], no studies have reported autophagy in FGSCs. In this report, we found that the synthetic compound C89 induced FGSC autophagy by inhibiting the activity of Akt and PI3K.…”

Section: Discussionmentioning

confidence: 99%

“…FGSCs have offered important opportunities for delaying menopause, understanding human oogenesis, and providing a new strategy for preserving fertility [2,5,6,7]. However, the biological activities and regulatory mechanisms of FGSCs, including in proliferation, differentiation, and apoptosis, are less well understood [8,9,10], and there has been no research about the autophagy of FGSCs.…”

Section: Introductionmentioning

confidence: 99%

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C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro

Tian

et al. 2019

Cells

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Postnatal female germline stem cells (FGSCs) are a type of germline stem cell with self-renewal ability and the capacity of differentiation toward oocyte. The proliferation, differentiation, and apoptosis of FGSCs have been researched in recent years, but autophagy in FGSCs has not been explored. This study investigated the effects of the small-molecule compound 89 (C89) on FGSCs and the underlying molecular mechanism in vitro. Cytometry, Cell Counting Kit-8 (CCK8), and 5-ethynyl-2’-deoxyuridine (EdU) assay showed that the number, viability, and proliferation of FGSCs were significantly reduced in C89-treated groups (0.5, 1, and 2 µM) compared with controls. C89 had no impact on FGSC apoptosis or differentiation. However, C89 treatment induced the expression of light chain 3 beta II (LC3BII) and reduced the expression of sequestosome-1 (SQSTM1) in FGSCs, indicating that C89 induced FGSC autophagy. To investigate the mechanism of C89-induced FGSC autophagy, RNA-seq technology was used to compare the transcriptome differences between C89-treated FGSCs and controls. Bioinformatics analysis of the sequencing data indicated a potential involvement of the phosphatidylinositol 3 kinase and kinase Akt (PI3K-Akt) pathway in the effects of C89′s induction of autophagy in FGSCs. Western blot confirmed that levels of p-PI3K and p-Akt were significantly reduced in the C89- or LY294002 (PI3K inhibitor)-treated groups compared with controls. Moreover, we found cooperative functions of C89 and LY294002 in inducing FGSC autophagy through suppressing the PI3K-Akt pathway. Taken together, this research demonstrates that C89 can reduce the number, viability, and proliferation of FGSCs by inducing autophagy. Furthermore, C89 induced FGSC autophagy by inhibiting the activity of PI3K and Akt. The PI3K-Akt pathway may be a target to regulate FGSC proliferation and death.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro

Tian

et al. 2019

Cells

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“…The germline stem cells were evaluated by the following experiments. Firstly, we determined the expression of Mvh (mouse vasa homolog, also termed DEAD box polypeptide 4, Ddx4) [46], Dazl (deleted in azoospermia-like) [47, 48], Fragilis (also termed interferon induced transmembrane protein 3, Ifitm3) [49], Oct4 (organic cation/carnitine transporter4, also termed POU domain, class 5, transcription factor 1, Pou5f1) [50], Stella (also termed developmental pluripotency-associated 3, Dppa3) [49, 51] and Blimp1 (also termed PR domain containing 1, with ZNF domain, Prdm1) [52] in SSCs and FGSCs that we isolated using RT-PCR analysis. The results showed that the cells express Mvh, Dazl, Fragilis, Oct4, Stella and Blimp1 (Supplementary Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

Systematic identification and comparison of expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in mouse germline stem cells

2017

Oncotarget

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Accumulating evidence indicates that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) involve in germ cell development. However, little is known about the functions and mechanisms of lncRNAs and circRNAs in self-renewal and differentiation of germline stem cells. Therefore, we explored the expression profiles of mRNAs, lncRNAs, and circRNAs in male and female mouse germline stem cells by high-throughput sequencing. We identified 18573 novel lncRNAs and 18822 circRNAs in the germline stem cells and further confirmed the existence of these lncRNAs and circRNAs by RT-PCR. The results showed that male and female germline stem cells had similar GDNF signaling mechanism. Subsequently, 8115 mRNAs, 3996 lncRNAs, and 921 circRNAs exhibited sex-biased expression that may be associated with germline stem cell acquisition of the sex-specific properties required for differentiation into gametes. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed different functions for these sex-biased lncRNAs and circRNAs. We further constructed correlated expression networks including coding–noncoding co-expression and competing endogenous RNAs with bioinformatics. Co-expression analysis showed hundreds of lncRNAs were correlated with sex differences in mouse germline stem cells, including lncRNA Gm11851, lncRNA Gm12840, lncRNA 4930405O22Rik, and lncRNA Atp10d. CeRNA network inferred that lncRNA Meg3 and cirRNA Igf1r could bind competitively with miRNA-15a-5p increasing target gene Inha, Acsl3, Kif21b, and Igfbp2 expressions. These findings provide novel perspectives on lncRNAs and circRNAs and lay a foundation for future research into the regulating mechanisms of lncRNAs and circRNAs in germline stem cells.

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“…Actually, ovary tissue possesses several types of somatic stem cells yet, for example, human OSE (ovarian surface epithelium) stem cells, which express SOX-2 and SSEA-4, but FGSCs do not, although they can form oocyte-like cells in culture, 420 and human VSELs, a very small embryonic-like stem cells with nuclear OCT4 expression and LGR5+, 421 , 422 in addition to Thecal stem cells and granulosa stem cells. 423 However, FGSCs are germline stem cells, which will be discussed as follows.…”

Section: Adult Germline Stem Cellsmentioning

confidence: 99%

Germline stem cells in human

Cheng

Shang

Zhou

2022

Sig Transduct Target Ther

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The germline cells are essential for the propagation of human beings, thus essential for the survival of mankind. The germline stem cells, as a unique cell type, generate various states of germ stem cells and then differentiate into specialized cells, spermatozoa and ova, for producing offspring, while self-renew to generate more stem cells. Abnormal development of germline stem cells often causes severe diseases in humans, including infertility and cancer. Primordial germ cells (PGCs) first emerge during early embryonic development, migrate into the gentile ridge, and then join in the formation of gonads. In males, they differentiate into spermatogonial stem cells, which give rise to spermatozoa via meiosis from the onset of puberty, while in females, the female germline stem cells (FGSCs) retain stemness in the ovary and initiate meiosis to generate oocytes. Primordial germ cell-like cells (PGCLCs) can be induced in vitro from embryonic stem cells or induced pluripotent stem cells. In this review, we focus on current advances in these embryonic and adult germline stem cells, and the induced PGCLCs in humans, provide an overview of molecular mechanisms underlying the development and differentiation of the germline stem cells and outline their physiological functions, pathological implications, and clinical applications.

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Stem Cells in Mammalian Gonads

Cited by 6 publications

References 100 publications

C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro

C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro

Systematic identification and comparison of expressed profiles of lncRNAs and circRNAs with associated co-expression and ceRNA networks in mouse germline stem cells

Germline stem cells in human

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