Three-Dimensional Retinal Organoids Facilitate the Investigation of Retinal Ganglion Cell Development, Organization and Neurite Outgrowth from Human Pluripotent Stem Cells.
Three-Dimensional Retinal Organoids Facilitate the Investigation of Retinal Ganglion Cell Development, Organization and Neurite Outgrowth from Human Pluripotent Stem Cells.
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DOI：
10.1038/s41598-018-32871-8
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发表时间：
2018-09-28
影响因子：
4.6
通讯作者：
Meyer JS
中科院分区：
文献类型：
--
作者：
Fligor CM;Langer KB;Sridhar A;Ren Y;Shields PK;Edler MC;Ohlemacher SK;Sluch VM;Zack DJ;Zhang C;Suter DM;Meyer JS
视网膜类器官是由人类多能干细胞（hPSCs）衍生的三维结构，它概括了视网膜的空间和时间分化，是视网膜发育的有效体外模型。然而，缺乏对视网膜神经节细胞（RGCs）在视网膜类器官内的发育和组织的重视。因此，在类器官发育的早期阶段，研究人员做出了初步的努力来表征RGC分化，明确定义的RGC层以一种暂时适当的方式发育，表达了RGC相关标记的补充。除了RGC发展的研究，视网膜类器官也可能被证明对细胞替代有用，其中广泛的轴突生长是达到突触后目标所必需的。类器官衍生的RGC可以帮助阐明促进轴突生长的因素，从而确定绕过RGC替代的巨大障碍的方法。因此，额外的努力表明，通过调节底物组成和生长因子信号传导，神经突生长显著增强。此外，类器官衍生的RGCs表现出多样化的表型，延伸出复杂的生长锥并表达大量的引导受体。总的来说，这些结果确立了视网膜类器官作为研究RGC发展的有价值的工具，并证明了类器官衍生的RGC作为研究影响类器官衍生的RGC神经突生长因素的有效平台的效用。
Retinal organoids are three-dimensional structures derived from human pluripotent stem cells (hPSCs) which recapitulate the spatial and temporal differentiation of the retina, serving as effective in vitro models of retinal development. However, a lack of emphasis has been placed upon the development and organization of retinal ganglion cells (RGCs) within retinal organoids. Thus, initial efforts were made to characterize RGC differentiation throughout early stages of organoid development, with a clearly defined RGC layer developing in a temporally-appropriate manner expressing a complement of RGC-associated markers. Beyond studies of RGC development, retinal organoids may also prove useful for cellular replacement in which extensive axonal outgrowth is necessary to reach post-synaptic targets. Organoid-derived RGCs could help to elucidate factors promoting axonal outgrowth, thereby identifying approaches to circumvent a formidable obstacle to RGC replacement. As such, additional efforts demonstrated significant enhancement of neurite outgrowth through modulation of both substrate composition and growth factor signaling. Additionally, organoid-derived RGCs exhibited diverse phenotypes, extending elaborate growth cones and expressing numerous guidance receptors. Collectively, these results establish retinal organoids as a valuable tool for studies of RGC development, and demonstrate the utility of organoid-derived RGCs as an effective platform to study factors influencing neurite outgrowth from organoid-derived RGCs.
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影响因子：
64.8
作者：
COHEN, J;BURNE, JF;BARTLETT, P
通讯作者：
BARTLETT, P
影响因子：
5.9
作者：
Gonzalez-Cordero A;Kruczek K;Naeem A;Fernando M;Kloc M;Ribeiro J;Goh D;Duran Y;Blackford SJI;Abelleira-Hervas L;Sampson RD;Shum IO;Branch MJ;Gardner PJ;Sowden JC;Bainbridge JWB;Smith AJ;West EL;Pearson RA;Ali RR
通讯作者：
Ali RR
影响因子：
16.2
作者：
Campbell, DS;Holt, CE
通讯作者：
Holt, CE
影响因子：
16.2
作者：
Deiner, MS;Kennedy, TE;Sretavan, DW
通讯作者：
Sretavan, DW
影响因子：
5.3
作者：
Crair, Michael C.;Mason, Carol A.
通讯作者：
Mason, Carol A.