Pharmacologic fibroblast reprogramming into photoreceptors restores vision

doi:10.1038/s41586-020-2201-4

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2201-4
	Pharmacologic fibroblast reprogramming into photoreceptors restores vision
	Jiang, Mingkai 1; Medlyn, Belinda E.1; Drake, John E.1,2; Duursma, Remko A.1; Anderson, Ian C.1; Barton, Craig V. M.1; Boer, Matthias M.1; Carrillo, Yolima 1; Castaneda-Gomez, Laura 1; Collins, Luke 1,3,4; Crous, Kristine Y.1; De Kauwe, Martin G.5,6,7; dos Santos, Bruna M.8,9; Emmerson, Kathryn M.10; Facey, Sarah L.1; Gherlenda, Andrew N.1; Gimeno, Teresa E.1,11,12; Hasegawa, Shun 1,13; Johnson, Scott N.1; Kannaste, Astrid 14; Macdonald, Catriona A.1; Mahmud, Kashif 1,15; Moore, Ben D.1; Nazaries, Loic 1; Neilson, Elizabeth H. J.8,9; Nielsen, Uffe N.1; Niinemets, Ulo 14; Noh, Nam Jin 1,16; Ochoa-Hueso, Raul 1,17; Pathare, Varsha S.1,18; Pendall, Elise 1; Pihlblad, Johanna 1; Pineiro, Juan 1,19; Powell, Jeff R.1; Power, Sally A.1; Reich, Peter B.1,20; Renchon, Alexandre A.1; Riegler, Markus 1; Rinnan, Riikka 21; Rymer, Paul D.1; Salomon, Roberto L.22; Singh, Brajesh K.1,23; Smith, Benjamin 1; Tjoelker, Mark G.1,24; Walker, Jennifer K. M.1; Wujeska-Klause, Agnieszka 1; Yang, Jinyan 1; Zaehle, Soenke 25; Ellsworth, David S.1
	2020-04-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	581 期号:7806 页码:83-+
文章类型	Article
语种	英语
国家	USA
英文关键词	Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision(1,2). Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-kappa B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision. A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000530868200013
WOS关键词	PLURIPOTENT STEM-CELLS ; MULLER GLIA ; RETINAL DEGENERATION ; VISUAL FUNCTION ; SMALL MOLECULES ; ROD ; EXPRESSION ; MOUSE ; DIFFERENTIATION ; ORGANOIDS
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281055
专题	地球科学资源环境科学气候变化
作者单位	1.Western Sydney Univ, Hawkesbury Inst Environm, Penrith, NSW, Australia; 2.SUNY Syracuse, Coll Environm Sci & Forestry, Dept Sustainable Resources Management, Syracuse, NY 13210 USA; 3.La Trobe Univ, Dept Ecol Environm & Evolut, Bundoora, Vic, Australia; 4.Arthur Rylah Inst Environm Res, Dept Environm Land Water & Planning, Heidelberg, Vic, Australia; 5.Univ New South Wales, ARC Ctr Excellence Climate Extremes, Sydney, NSW, Australia; 6.Univ New South Wales, Climate Change Res Ctr, Sydney, NSW, Australia; 7.Univ New South Wales, Evolut & Ecol Res Ctr, Sydney, NSW, Australia; 8.Univ Copenhagen, Dept Plant & Environm Sci, Plant Biochem Lab, Copenhagen, Denmark; 9.Univ Copenhagen, VILLUM Res Ctr Plant Plast, Copenhagen, Denmark; 10.CSIRO Oceans & Atmosphere, Climate Sci Ctr, Aspendale, Vic, Australia; 11.Basque Ctr Climate Change, Leioa, Spain; 12.Ikerbasque, Basque Fdn Sci, Bilbao, Spain; 13.Swedish Univ Agr Sci SLU, Dept Forest Ecol & Management, Umea, Sweden; 14.Estonian Univ Life Sci, Tartu, Estonia; 15.Indiana Univ, Dept Geog, Bloomington, IN 47405 USA; 16.Natl Inst Forest Sci, Forest Technol & Management Res Ctr, Pochon, South Korea; 17.Univ Cadiz, IVAGRO, Dept Biol, Campus Excelencia Int Agroalimentario CeiA3, Cadiz, Spain; 18.Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA; 19.West Virginia Univ, Div Plant & Soil Sci, Morgantown, WV 26506 USA; 20.Univ Minnesota, Dept Forest Resources, St Paul, MN 55108 USA; 21.Univ Copenhagen, Terr Ecol Sect, Dept Biol, Copenhagen, Denmark; 22.Univ Ghent, Fac Biosci Engn, Lab Plant Ecol, Ghent, Belgium; 23.Western Sydney Univ, Global Ctr Land Based Innovat, Penrith, NSW, Australia; 24.Lund Univ, Dept Phys Geog & Ecosyst Sci, Lund, Sweden; 25.Max Planck Inst Biogeochem, Jena, Germany
推荐引用方式 GB/T 7714	Jiang, Mingkai,Medlyn, Belinda E.,Drake, John E.,et al. Pharmacologic fibroblast reprogramming into photoreceptors restores vision[J]. NATURE,2020,581(7806):83-+.
APA	Jiang, Mingkai.,Medlyn, Belinda E..,Drake, John E..,Duursma, Remko A..,Anderson, Ian C..,...&Ellsworth, David S..(2020).Pharmacologic fibroblast reprogramming into photoreceptors restores vision.NATURE,581(7806),83-+.
MLA	Jiang, Mingkai,et al."Pharmacologic fibroblast reprogramming into photoreceptors restores vision".NATURE 581.7806(2020):83-+.