title: Wnt/β-catenin signaling triggers neuron reprogramming and regeneration in the mouse retina.
abstract: Cell-fusion-mediated somatic-cell reprogramming can be induced in culture; however, whether this process occurs in mammalian tissues remains enigmatic. Here, we show that upon activation of Wnt/β-catenin signaling, mouse retinal neurons can be transiently reprogrammed in vivo back to a precursor stage. This occurs after their spontaneous fusion with transplanted hematopoietic stem and progenitor cells (HSPCs). Moreover, we demonstrate that retinal damage is essential for cell-hybrid formation in vivo. Newly formed hybrids can proliferate, commit to differentiation toward a neuroectodermal lineage, and finally develop into terminally differentiated neurons. This results in partial regeneration of the damaged retinal tissue, with functional rescue. Following retinal damage and induction of Wnt/β-catenin signaling, cell-fusion-mediated reprogramming also occurs after endogenous recruitment of bone-marrow-derived cells in the eyes. Our data demonstrate that in vivo reprogramming of terminally differentiated retinal neurons after their fusion with HSPCs is a potential mechanism for tissue regeneration.
authors.affiliation: Center for Genomic Regulation CRG, 08003 Barcelona, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sanges
authors.forename: Neus
authors.initials: N
authors.lastname: Romo
authors.forename: Giacoma
authors.initials: G
authors.lastname: Simonte
authors.forename: Umberto
authors.initials: U
authors.lastname: Di Vicino
authors.forename: Ariadna Diaz
authors.initials: AD
authors.lastname: Tahoces
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D059467:Transcriptome; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D016202:N-Methylaspartate