Applying iPSCs for Preserving Endangered Species and Elucidating the Evolution of Mammalian Sex Determination

Abstract

The endangered species Tokudaia osimensis has the unique chromosome constitution of 2n = 25, with an XO/XO sex chromosome configuration (2n = 25; XO). There is urgency to preserve this species and to elucidate the regulator(s) that can discriminate the males and females arising from the indistinguishable sex chromosome constitution. However, it is not realistic to examine this rare animal species by sacrificing individuals. Recently, true naïve induced pluripotent stem cells were successfully generated from a female T. osimensis, and the sexual plasticity of its germ cells was elucidated. This achievement constitutes the basis of an attractive research area, including embryonic fate determination, sex determination, and factor(s) that can replace the Y chromosome. In this essay, concrete strategies to conserve rare animal species and to reveal their specific characteristics using other compatible and abundant animals are proposed.

Sexual dimorphism in brain transcriptomes of Amami spiny rats (Tokudaia osimensis): a rodent species where males lack the Y chromosome

“…The fact that ZFY and SRY are expressed in the brain of adult men shores up this possibility [62, 63]. Usage of induced pluripotent stem cells (iPSC) generated from this species might be useful in validating the current findings [92, 93]. Future work should compare current RNAseq results in the brain of Amami spiny rat to those obtained in Tokudaia species that possess sex chromosomes, e.g., Okinawa spiny rat ( Tokudaia muenninki ) [94–96], as this approach may reveal those genes/transcripts essential in sex determination in Amami spiny rat.…”

Anatomical templates for tissue (re)generation and beyond

“…In our view, iPS technology is an innovative tool which holds a high potential for biodiversity protection: (a) via cryopreservation of genetic material, (b) as a source of reprogrammed donor cells for nuclear transfer, (c) for directed differentiation to gametes in the future (Verma et al, 2012). Although iPSCs may prevent or reverse an extinction event, it is worth noting that animals developed via genomic manipulation technologies should not be released into their natural habitat due to their unknown impact on ecosystems (Honda, 2018).…”

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

“…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).…”

“…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.…”