000056821 001__ 56821
000056821 005__ 20200221144334.0
000056821 0247_ $$2doi$$a10.1172/JCI85193
000056821 0248_ $$2sideral$$a96386
000056821 037__ $$aART-2016-96386
000056821 041__ $$aeng
000056821 100__ $$aSanges, D.
000056821 245__ $$aReprogramming Müller glia via in vivo cell fusion regenerates murine photoreceptors
000056821 260__ $$c2016
000056821 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056821 5203_ $$aVision impairments and blindness caused by retinitis pigmentosa result from severe neurodegeneration that leads to a loss of photoreceptors, the specialized light-sensitive neurons that enable vision. Although the mammalian nervous system is unable to replace neurons lost due to degeneration, therapeutic approaches to reprogram resident glial cells to replace retinal neurons have been proposed. Here, we demonstrate that retinal Müller glia can be reprogrammed in vivo into retinal precursors that then differentiate into photoreceptors. We transplanted hematopoietic stem and progenitor cells (HSPCs) into retinas affected by photoreceptor degeneration and observed spontaneous cell fusion events between Müller glia and the transplanted cells. Activation of Wnt signaling in the transplanted HSPCs enhanced survival and proliferation of Müller- HSPC hybrids as well as their reprogramming into intermediate photoreceptor precursors. This suggests that Wnt signaling drives the reprogrammed cells toward a photoreceptor progenitor fate. Finally, Müller-HSPC hybrids differentiated into photoreceptors. Transplantation of HSPCs with activated Wnt functionally rescued the retinal degeneration phenotype in rd10 mice, a model for inherited retinitis pigmentosa. Together, these results suggest that photoreceptors can be generated by reprogramming Müller glia and that this approach may have potential as a strategy for reversing retinal degeneration.
000056821 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71984-ERC$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2015-71984$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2011-28580
000056821 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000056821 590__ $$a12.784$$b2016
000056821 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b4 / 128 = 0.031$$c2016$$dQ1$$eT1
000056821 592__ $$a8.31$$b2016
000056821 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000056821 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056821 700__ $$aSimonte, G.
000056821 700__ $$aDi Vicino, U.
000056821 700__ $$aRomo, N.
000056821 700__ $$0(orcid)0000-0003-0349-9997$$aPinilla, I.$$uUniversidad de Zaragoza
000056821 700__ $$aNicolás, M.
000056821 700__ $$aCosma, M.P.
000056821 7102_ $$11004$$2646$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Oftalmología
000056821 773__ $$g126, 8 (2016), 3104-3116$$pJ. clin. invest.$$tJOURNAL OF CLINICAL INVESTIGATION$$x0021-9738
000056821 8564_ $$s4998445$$uhttps://zaguan.unizar.es/record/56821/files/texto_completo.pdf$$yVersión publicada
000056821 8564_ $$s134374$$uhttps://zaguan.unizar.es/record/56821/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056821 909CO $$ooai:zaguan.unizar.es:56821$$particulos$$pdriver
000056821 951__ $$a2020-02-21-13:46:34
000056821 980__ $$aARTICLE