Presumptive germ cells derived from mouse pluripotent somatic cell hybrids

Lavagnolli, Thais M.C.; Fonseca, Silvia Moulin Ribeiro; Serafim, Rui C.; Pereira, Virgínia S.; Santos, Enrico Jardim Clemente; Abdelmassih, S.; Kerkis, Alexandre; Kerkis, Irina

doi:10.1016/j.diff.2009.07.003

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…Germ cell differentiation is a cytological feature common to pluripotent stem cell lines (Wakayama et al, 2001; Kanatsu‐Shinohara et al, 2004; Eguizabal et al, 2009; Hayashi and Surani, 2009; Lavagnolli et al, 2009). The iPS cells—the new face of pluripotent stem cells—also possess the potential to differentiate into germ cells when placed in the proper environment in vivo (Okita et al, 2007; Zhao et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Induction of primordial germ cells from mouse induced pluripotent stem cells derived from adult hepatocytes

et al. 2010

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Pluripotent stem cells can be established by various methods, but they share several cytological properties, including germ cell differentiation in vitro, independently of their origin. Although mouse induced pluripotent stem (iPS) cells can produce functional gametes in vivo, it is still unclear whether or not they have the ability to produce presumptive germ cells in vitro. Here, we show that mouse iPS cells derived from adult hepatocytes were able to differentiate into presumptive germ cells marked by mouse vasa homolog (Mvh) expression in feeder-free or suspension cultures. Embryoid body (EB) formation from iPS cells also induced the formation of round-shaped cells resembling immature oocytes. Mvh(+) cells formed clumps by co-aggregation with differentiation-supporting cells, and increased expression of germ cell markers was detected in these cell aggregates. Differentiation culture of presumptive germ cells from iPS cells could provide a conventional system for facilitating our understanding of the mechanisms underlying direct reprogramming and germline competency.

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Section: Discussionmentioning

confidence: 99%

Induction of primordial germ cells from mouse induced pluripotent stem cells derived from adult hepatocytes

et al. 2010

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“…Despite increasing reports of oocyte-like cell differentiation from pluripotent stem cells in vitro [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [37], little is known about the underlying mechanisms prohibiting their normal development, owing to the low efficiency and reproducibility of differentiation. To date, only a few studies have focused on the abnormalities commonly observed in ESC-derived oocytes, demonstrating the absence of meiotic chromosomal organization and its associated proteins in mouse ESC-derived FLSs [20], [28], [38].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies have also demonstrated FLS differentiation from XY and XX mouse ESCs [20], [21], [22], [23], although the FLSs had the appearance of primary-to-secondary follicles and antrum formation was not observed. In other studies, oocyte-like cells were generated but FLSs were not formed [22], [24], [25], [26], [27], [28]. Thus, it appears that there are crucial obstacles to the development of folliculogenesis from pluripotent stem cells in culture, especially beyond the secondary follicle stage [14].…”

Section: Introductionmentioning

confidence: 92%

Aberrant Gene Expression and Sexually Incompatible Genomic Imprinting in Oocytes Derived from XY Mouse Embryonic Stem Cells In Vitro

et al. 2013

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Mouse embryonic stem cells (ESCs) have the potential to differentiate into germ cells (GCs) in vivo and in vitro. Interestingly, XY ESCs can give rise to both male and female GCs in culture, irrespective of the genetic sex. Recent studies showed that ESC-derived primordial GCs contributed to functional gametogenesis in vivo; however, in vitro differentiation techniques have never succeeded in generating mature oocytes from ESCs due to cryptogenic growth arrest during the preantral follicle stages of development. To address this issue, a mouse ESC line, capable of producing follicle-like structures (FLSs) efficiently, was established to investigate their properties using conventional molecular biological methods. The results revealed that the ESC-derived FLSs were morphologically similar to ovarian primary-to-secondary follicles but never formed an antrum; instead, the FLSs eventually underwent abnormal development or cell death in culture, or formed teratomas when transplanted under the kidney capsule in mice. Gene expression analyses demonstrated that the FLSs lacked transcripts for genes essential to late folliculogenesis, including gonadotropin receptors and steroidogenic enzymes, whereas some other genes were overexpressed in FLSs compared to the adult ovary. The E-Cadherin protein, which is involved in cell-to-cell interactions, was also expressed ectopically. Remarkably, it was seen that oocyte-like cells in the FLSs exhibited androgenetic genomic imprinting, which is ordinarily indicative of male GCs. Although the FLSs did not express male GC marker genes, the DNA methyltransferase, Dnmt3L, was expressed at an abnormally high level. Furthermore, the expression of sex determination factors was ambiguous in FLSs as both male and female determinants were expressed weakly. These data suggest that the developmental dysfunction of the ESC-derived FLSs may be attributable to aberrant gene expression and genomic imprinting, possibly associated with uncertain sex determination in culture.

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“…hIDPSCs are known to express both mesenchymal stem cell markers (SH2, SH3 and SH4) and human embryonic stem cell markers (OCT 4, NANOG, SSEA-3 and SSEA-4) (Gomes et al, 2010). Furthermore, hIDPSCs have a normal karyotype and show the capacity for multilineage differentiation into neurons, smooth and skeletal muscle, cartilage, bone, and other cell types ex vivo and in vivo (Kerkis et al, 2006, Lavagnolli et al, 2009. Limited studies have been performed to test dental pulp stem cells as potential treatment for LSCD.…”

Section: Dental Pulp Stem Cellsmentioning

confidence: 99%