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从多能细胞生成功能性眼睛。

Generation of functional eyes from pluripotent cells.

作者信息

Viczian Andrea S, Solessio Eduardo C, Lyou Yung, Zuber Michael E

机构信息

Department of Ophthalmology, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, United States of America.

出版信息

PLoS Biol. 2009 Aug;7(8):e1000174. doi: 10.1371/journal.pbio.1000174. Epub 2009 Aug 18.

Abstract

Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.

摘要

多能细胞,如胚胎干细胞(ES)和诱导多能干细胞(iPS),是生成器官特异性细胞类型的起点。例如,将多能细胞转化为视网膜细胞可为治疗视网膜损伤和退行性病变提供机会。在本研究中,我们采用体内策略来确定是否可以从特定群体的非洲爪蟾多能细胞生成功能性视网膜。从囊胚期胚胎分离的动物极细胞是多能的。未经处理时,这些细胞移植到侧翼或眼区后仅形成表皮。相比之下,七种转录因子的错误表达诱导了视网膜细胞类型的形成。诱导产生的视网膜细胞在移植到发育中胚胎的侧翼时形成眼睛,从而确定其为视网膜谱系。当内源性眼区被诱导产生的视网膜细胞取代时,它们形成的眼睛在分子、解剖和电生理方面与正常眼睛相似。重要的是,诱导产生的眼睛能够引导基于视觉的行为。这些结果表明,多能细胞的命运可能会被有意改变,以产生多能视网膜祖细胞,后者分化为功能性视网膜细胞类别并形成足以实现视觉的神经回路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b41e/2716519/54736b36724e/pbio.1000174.g001.jpg

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