Generation of functional eyes from pluripotent cells.
Generation of functional eyes from pluripotent cells.
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DOI：
10.1371/journal.pbio.1000174
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发表时间：
2009-08
期刊：
影响因子：
9.8
通讯作者：
Zuber ME
中科院分区：
文献类型：
--
作者：
Viczian AS;Solessio EC;Lyou Y;Zuber ME
多能细胞定向分化为特定细胞类型是再生医学的主要障碍。这项研究表明，眼区转录因子因子可以指导多能细胞进入功能蛙眼。多能细胞如胚胎干（ES）和诱导多能干（iPS）细胞是产生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以提供治疗视网膜损伤和变性的机会。在这项研究中，我们使用了一种体内策略，以确定是否可以从一个确定的多能非洲爪蟾细胞群产生功能性视网膜。从囊胚期胚胎分离的动物极细胞是多能的。未经处理，这些细胞仅形成表皮，当移植到侧腹或眼区时。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。诱导的视网膜细胞在移植到发育中的胚胎侧腹时形成眼睛，从而形成视网膜谱系。当内源性视野被诱导的视网膜细胞取代时，它们形成的眼睛在分子上、解剖学上和电生理学上与正常眼睛相似。重要的是，诱导的眼睛可以引导基于视觉的行为。这些结果表明，多能细胞的命运可能被故意改变，以产生多能视网膜祖细胞，其分化成功能性视网膜细胞类别，并形成足以维持视力的神经回路。再生医学的目标是取代死亡或垂死的细胞。成功的细胞替代取决于供体细胞分化成靶器官中丢失的所有功能细胞类型的能力。例如，视网膜疾病或损伤导致的失明需要更换视网膜中发现的多达七种专门细胞类型。多能细胞最著名的特征是它们能够分化成任何成体细胞类型。然而，这一定义性特征提出了确定其转化为组织修复所需的细胞类型的条件的挑战。我们想知道，多能细胞是否可以被定向生成青蛙非洲爪蟾（Xenopus laevis）形成功能性眼睛所必需的所有视网膜细胞类型。如果不进行治疗，移植的多能细胞只能形成皮肤的表皮层。然而，当被迫表达眼场转录因子（EFTF）基因时，这些细胞分化成所有七种视网膜细胞类别，并最终将自己组织成一只功能正常的眼睛，可以检测光线并以基于视觉的行为引导蝌蚪。我们的研究结果表明，多能细胞可以被有目的地改变，以产生视力所需的所有功能性视网膜细胞类别。
The directed differentiation of pluripotent cells into specific cell-types is a major hurdle in regenerative medicine. This study shows the eye field transcription factor factors can direct pluripotent cells into functioning frog eyes. 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. The goal of regenerative medicine is to replace dead or dying cells. Successful cell replacement depends on the ability of donor cells to differentiate into all functional cell types lost in the target organ. Blindness resulting from retinal disease or damage, for example, would require the replacement of as many as seven specialized cell types found in the retina. The most celebrated characteristic of pluripotent cells is their ability to differentiate into any adult cell type. This defining feature, however, presents the challenge of identifying the conditions for their conversion to the cell types needed for tissue repair. We asked if pluripotent cells could be directed to generate all the retinal cell types necessary to form a functional eye in the frog, Xenopus laevis. If left untreated, transplanted pluripotent cells only form the epidermal layer of the skin. However, when forced to express the eye field transcription factor (EFTF) genes, the cells differentiate into all seven retinal cell classes and eventually organize themselves into a functioning eye that can detect light and guide tadpoles in a vision-based behavior. Our results demonstrate that pluripotent cells can be purposely altered to generate all the functional retinal cell classes necessary for sight.
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DOI：
10.1016/s0305-0491(00)00195-4
发表时间：
2000-06-01
影响因子：
2.2
作者：
Asashima, M;Ariizumi, T;Malacinski, GM
通讯作者：
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影响因子：
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作者：
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作者：
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King, HD
影响因子：
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作者：
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通讯作者：
Perron, Muriel
影响因子：
2.5
作者：
CONSTANTINEPATON, M;CAPRANICA, RR
通讯作者：
CAPRANICA, RR