Oral Presentation 6th Annual Meeting for Australasian Society for Stem Cell Research 2013

FGF/ERK Signalling Induces X Chromosome Inactivation in LIF-dependent Equine Induced Pluripotent Stem Cells (#16)

Deanne J Whitworth 1 , Dmitry A Ovchinnikov 2 , Jane Sun 2 , Patrick RJ Fortuna 2 , Ernst J Wolvetang 2
  1. School of Veterinary Science, University of Queensland, Gatton, Qld, Australia
  2. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Qld, Australia

In this study we have reprogrammed dermal fibroblasts from an adult female horse into induced pluripotent stem cells (equiPSCs) that are LIF-dependent and have two active X chromosomes (XaXa). This naïve XaXa pluripotent state is stable and has been maintained for more than 36 passages, with the cells undergoing X chromosome inactivation (XCI) when allowed to differentiate. Further, we demonstrate that FGF/ERK signalling in these equiPSCs initiates XCI, as evidenced by immunostaining for trimethylation of histone H3K27 and expression of XIST, reflecting a shift to a more primed, rather than naïve, state of pluripotency. We also show that FGF signalling has a proliferative effect on equiPSCs independent of FGF/ERK signalling. Thus, equiPSCs constitute a comparative model to the existing, and disparate, human and mouse models and provide novel insights into XCI, the mechanisms that confer naïve, versus primed, pluripotency and the role of FGF signalling in pluripotent stem cells.