Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina

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 sta...

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Main Authors: Daniela Sanges, Neus Romo, Giacoma Simonte, Umberto Di Vicino, Ariadna Diaz Tahoces, Eduardo Fernández, Maria Pia Cosma
Format: Article
Language:English
Published: Elsevier 2013-07-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124713002933
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author Daniela Sanges
Neus Romo
Giacoma Simonte
Umberto Di Vicino
Ariadna Diaz Tahoces
Eduardo Fernández
Maria Pia Cosma
author_facet Daniela Sanges
Neus Romo
Giacoma Simonte
Umberto Di Vicino
Ariadna Diaz Tahoces
Eduardo Fernández
Maria Pia Cosma
author_sort Daniela Sanges
collection DOAJ
description 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.
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spelling doaj.art-94fbb341dd184b21aca0ea2bf56d6c582022-12-21T18:27:22ZengElsevierCell Reports2211-12472013-07-014227128610.1016/j.celrep.2013.06.015Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse RetinaDaniela Sanges0Neus Romo1Giacoma Simonte2Umberto Di Vicino3Ariadna Diaz Tahoces4Eduardo Fernández5Maria Pia Cosma6Center for Genomic Regulation (CRG), 08003 Barcelona, SpainCenter for Genomic Regulation (CRG), 08003 Barcelona, SpainCenter for Genomic Regulation (CRG), 08003 Barcelona, SpainCenter for Genomic Regulation (CRG), 08003 Barcelona, SpainBioengineering Institute, University Miguel Hernández and CIBER BBN, 03202 Elche (Alicante), SpainBioengineering Institute, University Miguel Hernández and CIBER BBN, 03202 Elche (Alicante), SpainCenter for Genomic Regulation (CRG), 08003 Barcelona, SpainCell-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.http://www.sciencedirect.com/science/article/pii/S2211124713002933
spellingShingle Daniela Sanges
Neus Romo
Giacoma Simonte
Umberto Di Vicino
Ariadna Diaz Tahoces
Eduardo Fernández
Maria Pia Cosma
Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
Cell Reports
title Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
title_full Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
title_fullStr Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
title_full_unstemmed Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
title_short Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
title_sort wnt β catenin signaling triggers neuron reprogramming and regeneration in the mouse retina
url http://www.sciencedirect.com/science/article/pii/S2211124713002933
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