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 are studying 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. Furthermore, we are carrying out studies to test whether cell-fusion mediated reprogramming is an efficient therapy for Parkinson’s disease, and if it is a mechanism that controls liver regeneration, an organ with high regenerative capacity in mammals. Three manuscripts are currently under revision for these projects. We are also investigating the mechanisms controlling cell-to-cell fusion, and how ploidy is controlled in reprogrammed hybrids.