Reprogramming of germ cells into pluripotency

Sekita, Yoichi; Nakamura, Toshinobu; Kimura, Tohru

doi:10.4252/wjsc.v8.i8.251

Cited by 13 publications

(15 citation statements)

References 94 publications

(108 reference statements)

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“…This outcome shows that various mechanisms can synergize their effects in the reprogramming of PGCs. It has also been reported that mutations in genes involved in PGC development, such as Dnd1, Pten, and Pgct1, improve EGC derivation efficiency [19].…”

Section: Non-classical Pgc Reprogrammingmentioning

confidence: 98%

“…The Kit signaling pathway can also be implicated in the origin of human ECCs. Both KIT and Kit ligand (stem cell factor) mutations are related to human teratomas [19].…”

Section: Pgc Reprogramming In Vivomentioning

confidence: 99%

“…Several signaling pathways and genes have been shown to be implicated, such as Blimp1 downregulation, PTEN inactivation, Klf4, and c-Myc upregulation, PI3K/Akt signaling activation, and transforming growth factor (TGF)β signaling, among others [21,[39][40][41]. Most of these mechanisms are also involved in iPSC derivation, indicating a common regulatory network between the various reprogramming processes [19].…”

Section: Classical Pgc Reprogramming Mechanismmentioning

confidence: 99%

“…Akt, one of the primary factors related to the reprogramming of PGCs, as noted before, also promotes a more active chromatin, mainly by inhibition of Mbd3, a component of the nucleosome remodeling deacetylase complex. Mbd3 is important in heterochromatin formation, and its inhibition promotes reprogramming in both EGC and iPSC derivation [19].…”

Section: Germ Cellmentioning

confidence: 99%

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Primordial Germ Cell Reprogramming

Miguel¹,

Alcaina²,

Maza³

2018

Germ Cell

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Primordial germ cells (PGCs) are the embryonic precursors of the gametes. Thus, they are unipotent cells. However, PGCs share some common features with pluripotent stem cells. Among them, PGCs show alkaline phosphatase activity and express stage-specific embryonic antigens and pluripotency factors Lin28, Oct4, Sox2, and Nanog. Under specific conditions, they undergo spontaneous reprogramming in vivo. Moreover, they can be easily reprogrammed in vitro into pluripotent embryonic germ cells (EGCs) by culturing them in the presence of basic fibroblast growth factor or the epigenetic modulator trichostatin A. Previous work in our laboratory has also proven that hypoxia alone can reprogram PGCs into hypoxia-induced embryonic germ-like cells, which have a pluripotent phenotype but which do not show self-renewal capacity. Therefore, PGCs are an interesting model to further comprehensively understand the process of cell reprogramming. This chapter reviews various methods to achieve PGC reprogramming, as well as the molecular pathways involved. We focus on soluble factors and genetic strategies to obtain pluripotent cells from PGCs. Special emphasis will be given to factors implied in energetic metabolism, epigenetics, and cell signaling transduction, both in vitro and in vivo.

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Section: Non-classical Pgc Reprogrammingmentioning

confidence: 98%

“…The Kit signaling pathway can also be implicated in the origin of human ECCs. Both KIT and Kit ligand (stem cell factor) mutations are related to human teratomas [19].…”

Section: Pgc Reprogramming In Vivomentioning

confidence: 99%

Section: Classical Pgc Reprogramming Mechanismmentioning

confidence: 99%

Section: Germ Cellmentioning

confidence: 99%

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Primordial Germ Cell Reprogramming

Miguel¹,

Alcaina²,

Maza³

2018

Germ Cell

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“…This inter-relationship is of particular importance. Primordial germ cells are the precursors to all gametes as the founder cells of the germline, and can be reprogrammed into both pluipotent stem cells or germ cell tumors, such as testicular teratomas [140].…”

Section: Effects Of the Failure Of Exteriorization Of The Testes On Tmentioning

confidence: 99%

Reappraising the exteriorization of the mammalian testes through evolutionary physiology

Miller

Torday

2019

Communicative & Integrative Biology

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A number of theories have been proposed to explain the exteriorization of the testicles in most mammalian species. None of these provide a consistent account for the wide variety of testicular locations found across the animal kingdom. It is proposed that testicular location is the result of coordinate action of testicular tissue ecologies to sustain preferential states of homeostatic equipoise throughout evolutionary development in response to the advent of endothermy.

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Selective elimination of pluripotent stem cells by PIKfyve specific inhibitors

et al. 2022

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Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their ability to form teratocarcinomas in mice, and intraperitoneal injections of WX8 into mice harboring teratocarcinoma xenografts selectively eliminated pluripotent cells. Differentiated cells continued to proliferate, but at a reduced rate. These results provide a proof of principle that PIKfyve specific inhibitors can selectively eliminate pluripotent stem cells in vivo as well as in vitro.

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Reprogramming of germ cells into pluripotency

Cited by 13 publications

References 94 publications

Primordial Germ Cell Reprogramming

Primordial Germ Cell Reprogramming

Reappraising the exteriorization of the mammalian testes through evolutionary physiology

Selective elimination of pluripotent stem cells by PIKfyve specific inhibitors

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