RESUMEN
Human infertility is a complex disorder at the genetic, molecular, cellular, organ, and hormonal levels. New developing technology based on the generation of human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) might improve understanding of early germ cell development (specification, migration, gametogenesis, and epigenetic reconstitutions), as well as offering a solution for infertility and hereditary disorders. In this study, we differentiated hiPSCs with trisomy 21 into hPGCLCs. In vitro-derived germ cells from hiPSCs with Down syndrome (DS) express hPGCLC core circuitry, EOMES, SOX17, and PRDM14 at relatively low levels. TFAP2C and PRDM1 were expressed and remained elevated, whereas NANOS3 and NANOG were downregulated in BMP4-induced hiPSCs with DS. The low level of NANOG and NANOS3 expression might negatively influence hPGCLC generation in DS hiPSCs. We suggest that DS hPGCLCs could be a suitable model for studying human early germ cell development, the epigenetic and molecular mechanisms of PGC specification and formation, as well as related infertility disorders, such as azoospermia and teratozoospermia.
Asunto(s)
Síndrome de Down , Células Madre Pluripotentes Inducidas , Diferenciación Celular/genética , Síndrome de Down/genética , Síndrome de Down/metabolismo , Regulación hacia Abajo , Células Germinativas/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismoRESUMEN
Primordial germ cells (PGCs) are a unique type of stem cells capable of giving rise to totipotent stem cells and ensuring the fertility of an organism and the transfer of its genome to the next generation. PGC research is an important perspective research field of developmental biology that handles many questions of embryogenesis and holds promise for treatments of infertility in the future. Considering ethical concerns related to human embryos, the main research approach in understanding the biology of human PGCs is in vitro studies. In this review, we consider the historical perspective of human PGC studies in vitro, the main existing models, and further outlooks and applications in medicine and science.
