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Overcoming infertility with Induced Pluripotent Stem Cell Reprogramming?

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Review of “Fertile offspring from sterile sex chromosome trisomic mice” from Science by Stuart P. Atkinson

Chromosomal trisomy of the mammalian sex chromosomes represents the most common genetic cause of human infertility [1]; however, a team of researchers led by James M. A. Turner (Francis Crick Institute, London, UK) has discovered a potential means to rectify this unfortunate situation. 

In a new Science study, Hirota et al. describe how donor cells bearing three sex chromosomes lose an extra chromosome during somatic cell reprogramming, thereby generating healthy “properly-endowed” induced pluripotent stem cells (iPSCs) with the potential to yield functional sperm [2].

To study human infertility associated with sex chromosome trisomy (SCT), Hirota et al. first sought to generate iPSCs from fibroblasts derived from XXY and XYY mice for subsequent differentiation into primordial germ cell-like cells (PGCLCs). However, during the initial reprogramming process, the authors noted that a high proportion of SCT-derived iPSC lines lost one of their extra chromosomes, a phenomenon they dubbed trisomy-biased chromosome loss (TCL). Even more encouragingly, following transplantation into germ cell-deficient mouse testes, PGCLs differentiated from XY SCT-derived iPSCs yielded functional sperm with the ability to produce chromosomally normal, healthy, and fertile offspring!

But what about human patients? Reprogramming of human SCT patient fibroblasts did permit the generation of healthy hiPSCs with only two sex chromosomes, even with a reduced rate of TCL in comparison to mouse, suggesting that reprogramming could have relevancy in treating human infertility.

While the mechanisms that control TLC remain to be delineated, this exciting study does represent another great success for reprogramming; what more can iPSCs do?! To find out, stay up to date with the Stem Cells Portal!

References

  1. Heard, E. and J. Turner, Function of the sex chromosomes in mammalian fertility. Cold Spring Harb Perspect Biol 2011;3:a002675.
  2. Hirota, T., et al., Fertile offspring from sterile sex chromosome trisomic mice. Science 2017;357:932-935.