Similar morphological and molecular signatures shared by female and male germline stem cells

Xie, Wenhai; Wang, Hu; Wu, Ji

doi:10.1038/srep05580

Cited by 43 publications

(54 citation statements)

References 54 publications

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“…An anti-DDX4 antibody raised against the C-terminal 25 residues of human DDX4 (here onwards defined as DDX4 C25 antibody) has been used to isolate by MACS or FACS a small population of OSCs from adult ovary in mouse111213141718192025. The C-terminus shares high sequence homology between human and mouse, making this possible (Fig.…”

Section: Resultsmentioning

confidence: 99%

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FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

Zarate-Garcia

Lane

Merriman

et al. 2016

Sci Rep

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Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surface-bound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surface-bound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event.

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Section: Resultsmentioning

confidence: 99%

“…Previous studies have not reached a consensus over whether freshly sorted putative OSCs already express these germline markers, with some studies demonstrating expression111214171925 and others not1516.…”

Section: Resultsmentioning

confidence: 99%

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

Zarate-Garcia

Lane

Merriman

et al. 2016

Sci Rep

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“…Oogonial stem cells (OSCs, also termed FGSCs) with oogenic capacity were also successfully isolated and purified from adult mice and healthy reproductive-age women using fluorescence-activated cell sorting (FACS) with the same antibody13. We also showed similar morphological and molecular signatures shared by FGSCs and SSCs14. A growing body of research demonstrated that FGSCs could be achieved from mammalian ovary including mouse, rat, and human11121314151617181920212223242526.…”

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confidence: 80%

Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates

Ding

Liu

et al. 2016

Sci Rep

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Human female germline stem cells (FGSCs) have opened new opportunities for understanding human oogenesis, delaying menopause, treating infertility, and providing a new strategy for preserving fertility. However, the shortage of adult human ovaries tissues available impedes their future investigations and clinical applications. Here, we have established FGSC lines from scarce ovarian cortical tissues that exist in follicular aspirates (faFGSCs), which are produced and discarded in in vitro fertilization centers worldwide. The faFGSCs have characteristics of germline stem cells involved in the gene expression profile, growth characteristics, and a normal karyotype consistent with that of FGSCs obtained from ovarian cortexes surgically removed from patients (srFGSCs). Furthermore, faFGSCs have developmental potentials including spontaneous differentiation into oocytes under feeder-free conditions, communicating with granulosa cells by gap junctions and paracrine factors, entering meiosis after RA induction, as well as forming follicles after injection into human ovarian cortical tissues xenografted into adult immunodeficient female mice. Lastly, we developed a strategy guiding FGSCs differentiated into germinal vesicle (GV) stage oocytes in vitro and revealed their developmental mechanisms. Our study not only provides a new approach to obtain human FGSCs for medical treatment, but also opens several avenues to investigate human oogenesis in vitro.

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“…Although, compared with SSCs, less is known about FGSCs, an increasing number of research is now being focused on FGSCs [13, 6, 14]; in particular, the isolation and characterization of FGSCs from rat and human ovaries have allowed their biological functions and applications to be studied further [7, 15–17]. …”

Section: Introductionmentioning

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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Similar morphological and molecular signatures shared by female and male germline stem cells

Cited by 43 publications

References 54 publications

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates

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

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