Cell-fusion-mediated somatic cell reprogramming controlled by Wnt activity as a mechanism of neuron regeneration.
We have shown that upon activation of Wnt/b-catenin signalling, mouse retinal neurons can be transiently reprogrammed in vivo. These cells return to a precursor stage following their spontaneous fusion with transplanted haematopoietic stem and progenitor cells in damaged retinas. The newly formed hybrid cells reactivate neuronal precursor genes, and can thereby proliferate. The hybrids differentiate into neurons, which regenerate the damaged retinal tissue to provide functional rescue. Our data suggest that in-vivo reprogramming of terminally differentiated retinal neurons is a mechanism of tissue regeneration (Sanges et al., Cell Reports 2013).
We recently described retinal regeneration in rd10 mice, which is a model of retinitis pigmentosa, a severe disease that affects a large number of individuals and that results in progressive loss of vision (Sanges et al JCI 2010). Furthermore, we demonstrated cell-fusion mediated reprogramming as an efficient therapy for Parkinson’s disease, and as mechanism to control liver regeneration, an organ with high regenerative capacity in mammals (Altarche-Xifro et al eBiomedicine 2016; Pedone et al. Cell Reports 2017). We are also investigating the mechanisms controlling cell-to-cell fusion, and how ploidy is controlled in reprogrammed hybrids.