Modeling early retinal development with human embryonic and induced pluripotent stem cells
Modeling early retinal development with human embryonic and induced pluripotent stem cells
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DOI：
10.1073/pnas.0905245106
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发表时间：
2009-09-29
影响因子：
11.1
通讯作者：
Gamm, David M.
中科院分区：
文献类型：
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作者：
Meyer, Jason S.;Shearer, Rebecca L.;Gamm, David M.
人类多能干细胞有可能为人类个体发育的最早阶段提供全面的模型系统。为了发挥这一功能，这些细胞必须经历一个有针对性的、循序渐进的分化过程，遵循正常的发育时间表。在这里，我们证明了人类胚胎干细胞(HESCs)和诱导的多能干细胞(IPS)都有能力满足人类视网膜形成的这些要求。在分化后，hESCs最初产生了高度丰富的早期眼野细胞群。此后，一部分细胞获得了促进视网膜分化的特征，其序列和时间过程模仿了体内人类视网膜的发育。将这种培养方法应用于人iPS细胞系，也在体外产生了视网膜特异性细胞类型。最后，在分化过程中改变内源信号会以一种与早期神经和视网膜细胞命运决定的既定机制一致的方式影响谱系特异性基因的表达。这些发现应该有助于研究控制人类多能干细胞视网膜指定的分子事件。
Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis. Upon differentiation, hESCs initially yielded a highly enriched population of early eye field cells. Thereafter, a subset of cells acquired features of advancing retinal differentiation in a sequence and time course that mimicked in vivo human retinal development. Application of this culture method to a human iPS cell line also generated retina-specific cell types at comparable times in vitro. Lastly, altering endogenous signaling during differentiation affected lineage-specific gene expression in a manner consistent with established mechanisms of early neural and retinal cell fate determination. These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells.