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

Imamura, Makoto; Aoi, Takashi; Tokumasu, Ako; Mise, Nathan; Abe, Kuniya; Yamanaka, Shinya; Noce, Toshiaki

doi:10.1002/mrd.21223

Cited by 75 publications

(63 citation statements)

References 29 publications

(49 reference statements)

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“…In this regard, germ cells or primordial germ cells reported or claimed to have been derived from ES/iPS cells and epiblast cells [34][35][36][37] could be tested regarding their spermatogenic activity with our in vitro system. This particular application of our method would break the boundary between germ and somatic cells, and open a new phase in germ cell research.…”

Section: Discussionmentioning

confidence: 99%

In vitro production of fertile sperm from murine spermatogonial stem cell lines

et al. 2011

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spermatogonial stem cells (ssCs) are the only stem cells in the body that transmit genetic information to the next generation. The long-term propagation of rodent ssCs is now possible in vitro, and their genetic modification is feasible. However, their differentiation into sperm is possible only under in vivo conditions. Here we show a new in vitro system that can induce full spermatogenesis from ssC lines or any isolated ssCs. The method depends on an organ culture system onto which ssCs are transplanted. The settled ssCs form colonies and differentiate up into sperm. The resultant haploid cells are fertile, and give rise to healthy offspring through micro-insemination. In addition, the system can induce spermatogenesis from ssCs that show spermatogenic failure due to a micro-environmental defect in their original testes. Thus, an in vitro system is established that can be used to correct or manipulate the micro-environmental conditions required for proper spermatogenesis from murine ssC lines.

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Section: Discussionmentioning

confidence: 99%

In vitro production of fertile sperm from murine spermatogonial stem cell lines

et al. 2011

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“…The efficiency of differentiation from ES or iPS cells into haploid male germ cells is generally reported to be low. [14][15][16][17][18][19][20][21][22][23][24] Although there is no evidence for the speculation that this efficiency might be higher using AFS cells, to our opinion, the here reviewed knowledge warrants testing this new stem cell type for their usability for the in vitro investigation of sperm production (Figure 1).…”

Section: Amniotic Fluid Stem (Afs) Cells Could Be a Useful Tool To Stmentioning

confidence: 88%

“…from reprogramming of somatic cells also have been shown to differentiate into primordial germ cells and even to generate haploid germ cells. 5,[22][23][24] These pioneering studies allowed new important insights into the regulation of germ cell formation in vitro.…”

Section: Introductionmentioning

confidence: 99%

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

Gundacker¹,

Dolznig²,

Mikula³

et al. 2012

Asian J Androl

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Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem (AFS) cells as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

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“…As expected, the marmoset DDX4 promoter was hypomethylated in testis and sperm and highly methylated in somatic tissues (Figs 6 and 7). In contrast, marmoset ES cells exhibited hypermethylation of the DDX4 promoter, unlike mouse ES cells, but similar to some induced pluripotent stem cell lines (Imamura et al 2006(Imamura et al , 2010. Consequently, we focused on the Octamer/Sox elements, which are known to exhibit spermatogenic cell-specific DNA hypermethylation in mouse (Imamura et al 2006, Farthing et al 2008, Western et al 2010.…”

Section: Dna Methylation Profile Unique To Marmoset Spermatogenic Cellsmentioning

confidence: 98%

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

Lin

Imamura²,

Sano³

et al. 2012

Reproduction

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Germ cell development is a fundamental process required to produce offspring. The developmental program of spermatogenesis has been assumed to be similar among mammals. However, recent studies have revealed differences in the molecular properties of primate germ cells compared with the well-characterized mouse germ cells. This may prevent simple application of rodent insights into higher primates. Therefore, thorough investigation of primate germ cells is necessary, as this may lead to the development of more appropriate animal models. The aim of this study is to define molecular signatures of spermatogenic cells in the common marmoset, Callithrix jacchus. Interestingly, NANOG, PRDM1, DPPA3 (STELLA), IFITM3, and ZP1 transcripts, but no POU5F1 (OCT4), were detected in adult marmoset testis. Conversely, mouse testis expressed Pou5f1 but not Nanog, Prdm1, Dppa3, Ifitm3, and Zp1. Other previously described mouse germ cell markers were conserved in marmoset and mouse testes. Intriguingly, marmoset spermatogenic cells underwent dynamic protein expression in a developmental stage-specific manner; DDX4 (VASA) protein was present in gonocytes, diminished in spermatogonial cells, and reexpressed in spermatocytes. To investigate epigenetic differences between adult marmoset and mice, DNA methylation analyses identified unique epigenetic profiles to marmoset and mice. Marmoset NANOG and POU5F1 promoters in spermatogenic cells exhibited a methylation status opposite to that in mice, while the DDX4 and LEFTY1 loci, as well as imprinted genes, displayed an evolutionarily conserved methylation pattern. Marmosets have great advantages as models for human reproductive biology and are also valuable as experimental nonhuman primates; thus, the current study provides an important platform for primate reproductive biology, including possible applications to humans.

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

Cited by 75 publications

References 29 publications

In vitro production of fertile sperm from murine spermatogonial stem cell lines

In vitro production of fertile sperm from murine spermatogonial stem cell lines

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

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