Differences and similarities in the developmental status of embryo‐derived stem cells and primordial germ cells revealed by global expression profiling

Mise, Nathan; Fuchikami, Takuya; Sugimoto, Michihiko; Kobayakawa, Satoru; Ike, Fumio; Ogawa, Takehiko; Tada, Takashi; Kanaya, Shigehiko; Noce, Toshiaki; Abe, Kuniya

doi:10.1111/j.1365-2443.2008.01211.x

Cited by 47 publications

(42 citation statements)

References 55 publications

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“…6). It has been reported that transcriptome characteristics of PGCs are different from those of pluripotent cells [38]. Our microarray data uncovered the sequential changes in transcription during the conversion of PGCs to pluripotent cells.…”

Section: Pluripotent Candidate Cells Progress S Phase Of Cell Cycle Amentioning

confidence: 64%

Tracing the Conversion Process from Primordial Germ Cells to Pluripotent Stem Cells in Mice1

Nagamatsu

Kosaka

Saito

et al. 2012

Biology of Reproduction

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To understand mechanisms underlying acquisition of pluripotency, it is critical to identify cells that can be converted to pluripotent stem cells. For this purpose, we focused on unipotent primordial germ cells (PGCs), which can be reprogrammed into pluripotent embryonic germ (EG) cells under defined conditions. Treatment of PGCs with combinations of signaling inhibitors, including inhibitors of MAP2K (MEK), GSK3B (GSK-3beta), and TGFB (TGFbeta) type 1 receptors, induced cells to enter a pluripotent state at a high frequency (12.1%) by Day 10 of culture. When we employed fluorescence-activated cell sorting to monitor conversion of candidate cells to a pluripotent state, we observed a cell cycle shift to S phase, indicating enrichment of pluripotent cells, during the early phase of EG formation. Transcriptome analysis revealed that PGCs retained expression of some pluripotent stem cell-associated genes, such as Pou5f1 and Sox2, during EG cell formation. On the other hand, PGCs lost their germ lineage characteristics and acquired expression of pluripotent stem cell markers, such as Klf4 and Eras. The overall gene expression profiles revealed by this system provide novel insight into how pluripotency is acquired in germ-committed cells.

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Section: Pluripotent Candidate Cells Progress S Phase Of Cell Cycle Amentioning

confidence: 64%

Tracing the Conversion Process from Primordial Germ Cells to Pluripotent Stem Cells in Mice1

Nagamatsu

Kosaka

Saito

et al. 2012

Biology of Reproduction

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“…In line with this notion, micro-array analyses have shown that many "PGC signature" genes (i.e. Dazl, Mvh and developmental pluripotency-associated protein 2, Dppa2) were not fully up-regulated in putative PGCs obtained from Mvh-LacZ or Mvh-GFP knock-in mouse ESCs (Mise et al, 2008).…”

Section: Discussionmentioning

confidence: 90%

Impaired meiotic competence in putative primordial germ cells produced from mouse embryonic stem cells

Tedesco

Farini²,

Felici³

2011

Int. J. Dev. Biol.

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There are still several unanswered questions and problems about the recently claimed possibility of producing functional germ cells in vitro from pluripotent embryonic stem cells (ESCs). In the present paper, we compared by single-cell analysis the capability of putative primordial germ cells (PGCs), produced in vitro from ESCs, and that of endogenous PGCs isolated from embryos, to enter and progress through meiotic prophase I. Using a protocol previously reported to be suitable to produce female germ cells from mouse ESC monolayers, we first identified putative PGCs by analysing the expression pattern of several markers such as SSEA1, APase, OCT4, NANOG, MVH and SCP3 of pre-and post migratory PGCs. Next, after isolation of such cells from culture, we tested their meiotic capability. The evaluation at 2-5 days of culture of the number of cells showing meiotic nuclear SCP3 staining in cytospreads showed that it remained nearly constant in the putative PGCs, whereas it increased markedly in endogenous PGCs. Moreover, we observed that in putative PGCs, the nuclear distribution or expression of SCP3 and other meiotic markers such as DMC1,     H2AX and SCP1 were always highly abnormal in comparison to that observed in endogenous cultured PGCs. We conclude that although the formation of cells showing characteristics of PGCs can occur efficiently from ESCs in vitro, these cells possess impaired capability to enter and progress through meiotic prophase I. KEY WORDS: embryonic stem cell, gametogenesis, meiosis, primordial germ cellFrom the first report by Hübner et al. (2003) showing that XY mouse embryonic stem cells (mESCs) are able to produce follicleenclosed growing oocytes, several studies have described the in vitro differentiation of female and male germ cells from mouse and human ESCs (hESC) in either the monolayer or the embryoid bodies (EBs) culture method (for reviews see Hua and Sidhu, 2008;Nagano, 2007;Aflatoonian and Moore, 2006). The experiments carried out to produce germ cells from ESCs are based on years of intense investigations on the in vivo and in vitro development of mouse primordial germ cells (PGCs), the oocyte and sperm precursors (for reviews see De Felici et al., 2004;De Felici, 2001). In particular the recent progress in elucidating the process of germ line specification in mammals (Ohinata et al., 2009 and references herein) and the possibility to mimic in vitro events of later PGC development including entering into meiosis (Farini et al., 2005), have given precious information for the derivation and characterization of germ cells produced from ESCs.In the mouse embryo, PGC development occurs in about 7Int. J. Dev. Biol. 55: 215-222 (2011) days, from around 5.5 days post coitus (dpc), when the first inductive events of the germ cell lineage occur in the epiblast, to 12.5 dpc when sex differentiation of PGCs into meiotic oocytes in the female and G0-arrested prospermatogoni/gonocytes in maleoccur (for a review, see Western, 2009). Elegant recent studies have shown that m...

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“…In those studies, however, the latest developmental stage analyzed was 10.5 dpc, identifying genes expressed very early during PGC development. Two microarray experiments have analyzed the transcriptomes of male and female germ cells isolated at 11.5, 12.5, and 13.5 dpc [30] or of pooled XX and XY germ cells isolated at 10.5 and 12.5 dpc [29], yielding potential insights into early germ cell differentiation events. However, because these studies did not include somatic controls, they did not identify germ cell-specific genes.…”

Section: Methodological Considerations and Comparisons To Previous Stmentioning

confidence: 99%

Uncovering Gene Regulatory Networks During Mouse Fetal Germ Cell Development

Rolland¹,

Lehmann²,

Johnson³

et al. 2010

Biology of Reproduction

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The commitment of germ cells to either oogenesis or spermatogenesis occurs during fetal gonad development: germ cells enter meiosis or mitotic arrest, depending on whether they reside within an ovary or a testis, respectively. Despite the critical importance of this step for sexual reproduction, gene networks underlying germ cell development have remained only partially understood. Taking advantage of the W(v) mouse model, in which gonads lack germ cells, we conducted a microarray study to identify genes expressed in fetal germ cells. In addition to distinguishing genes expressed by germ cells from those expressed by somatic cells within the developing gonads, we were able to highlight specific groups of genes expressed only in female or male germ cells. Our results provide an important resource for deciphering the molecular pathways driving proper germ cell development and sex determination and will improve our understanding of the etiology of human germ cell tumors that arise from dysregulation of germ cell differentiation.

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Differences and similarities in the developmental status of embryo‐derived stem cells and primordial germ cells revealed by global expression profiling

Cited by 47 publications

References 55 publications

Tracing the Conversion Process from Primordial Germ Cells to Pluripotent Stem Cells in Mice1

Tracing the Conversion Process from Primordial Germ Cells to Pluripotent Stem Cells in Mice1

Impaired meiotic competence in putative primordial germ cells produced from mouse embryonic stem cells

Uncovering Gene Regulatory Networks During Mouse Fetal Germ Cell Development

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