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iPSCs from an Endangered Mammalian Species Could Elucidate the Mechanism of Sex Determination with Evolutionary Y Chromosome Loss

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Since the successful derivation of induced pluripotent stem cells (iPSCs) in 2006, this strategy has been used to make what was once fantasy into reality. In this issue of BioEssays,… Click to show full abstract

Since the successful derivation of induced pluripotent stem cells (iPSCs) in 2006, this strategy has been used to make what was once fantasy into reality. In this issue of BioEssays, Honda proposes using iPSCs for preservation of endangered species, as exemplified by the Amami spiny rat, Tokudaia osimensis, which inhabits a small Japanese island. T. osimensis diverged from laboratory mouse and rat (Mus musculus and Rattus norvegicus) 14.5 million and 20.9 million years ago, respectively (http:// timetree.org). It subsequently lost the mammalian master sexdetermining gene, SRY, translocated the genes from the Y chromosome onto the X chromosome (including EIF2S3Y essential for spermatogenesis), and eliminated the entire Y chromosome, resulting in the same chromosomal constitution (2n1⁄4 25.XO) in males and females. Thus, T. osimensis provides a unique opportunity to explore the sex-determining mechanism in mammals without the XX/XY system. As this species is gravely endangered, sacrificing any animal for experimental purposes should be avoided. Honda et al. have generated true naïve iPSCs from tail biopsy of female T. osimensis, and produced interspecific chimeras by injecting the iPSCs into mouse blastocysts. Although the iPSCs differentiated into both male and female germ cells in chimeric testes and ovaries, respectively, their contributions were severely restricted, probably due to immunological or interspecific incompatibility between T. osimensis germ cells and host gonadal somatic cells. The article published in BioEssays proposes strategies for promoting iPSC-derived germline contribution in xenogenic hosts. T. osimensis iPSCs will be differentiated into PGC-like cells (PGCLCs) in vitro, which will then be aggregated with gonadal somatic cells and transplanted into immunodeficient mice. To make the gonadal cells compatible with PGCLCs, Sertoli (testicular-supporting) cells could be directly reprogrammed from T. osimensisfibroblasts.How this can be achieved is unclear as little is known about the genes involved in Sertoli cell differentiation in T. osimensis. No strategy is given for propagating iPSC-derived oocytes in chimeric ovaries. The author proposes an alternative strategy, named blastocyst complementation method, in which

Keywords: mechanism; ipscs endangered; sex; osimensis; chromosome

Journal Title: BioEssays
Year Published: 2018

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