Stem Cell Derived Retinal Pigment Epithelium: The Role of Pigmentation as Maturation Marker and Gene Expression Profile Comparison with Human Endogenous Retinal Pigment Epithelium.
Stem Cell Derived Retinal Pigment Epithelium: The Role of Pigmentation as Maturation Marker and Gene Expression Profile Comparison with Human Endogenous Retinal Pigment Epithelium.
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DOI：
10.1007/s12015-017-9754-0
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发表时间：
2017-10
影响因子：
4.8
通讯作者：
Bergen AA
中科院分区：
文献类型：
--
作者：
Bennis A;Jacobs JG;Catsburg LAE;Ten Brink JB;Koster C;Schlingemann RO;van Meurs J;Gorgels TGMF;Moerland PD;Heine VM;Bergen AA
在年龄相关性黄斑变性（AMD）中，视网膜色素上皮（RPE）恶化，导致光感受器衰退和严重的视力丧失。新的治疗策略旨在通过移植多能干细胞（PSC）衍生的RPE来替代RPE。已经开发了几种生成RPE的方案，其中色素沉着的外观通常被用作RPE分化和成熟的指标。然而，目前尚不清楚不同的色素沉着阶段如何反映psc来源的RPE细胞的发育阶段和功能。我们制备了人类胚胎干细胞衍生的RPE （hESC-RPE）细胞，并研究了它们在早期色素沉着（EP）和晚期色素沉着（LP）阶段的基因表达谱。此外，我们将hESC-RPE样品与人内源性RPE进行了比较。我们使用通用参考设计微阵列（44 K）。我们的分析表明，成熟的hESC-RPE在获得色素沉着后，表达了人类RPE特有的标记物。有趣的是，我们的分析显示EP和LP hESC-RPE在基因表达上没有太大差异。我们的数据进一步表明，色素hESC-RPE在视觉循环和氧化应激途径中的表达明显低于人内源性RPE。相反，我们观察到与发育上皮细胞典型的过程粘附到极性模型相关的途径的表达显著增加。我们的结论是，在体外，色素沉着的首次出现标志着分化的RPE。然而，色素沉着的进一步增加并不会导致显著的基因表达变化，也不会增加重要的RPE功能。因此，我们的结果表明，获得适合移植的分化hESC-RPE细胞的时间跨度可能会大大缩短。本文的在线版本（doi:10.1007/s12015-017-9754-0）包含补充资料，仅供授权用户使用。
In age-related macular degeneration (AMD) the retinal pigment epithelium (RPE) deteriorates, leading to photoreceptor decay and severe vision loss. New therapeutic strategies aim at RPE replacement by transplantation of pluripotent stem cell (PSC)-derived RPE. Several protocols to generate RPE have been developed where appearance of pigmentation is commonly used as indicator of RPE differentiation and maturation. It is, however, unclear how different pigmentation stages reflect developmental stages and functionality of PSC-derived RPE cells. We generated human embryonic stem cell-derived RPE (hESC-RPE) cells and investigated their gene expression profiles at early pigmentation (EP) and late pigmentation (LP) stages. In addition, we compared the hESC-RPE samples with human endogenous RPE. We used a common reference design microarray (44 K). Our analysis showed that maturing hESC-RPE, upon acquiring pigmentation, expresses markers specific for human RPE. Interestingly, our analysis revealed that EP and LP hESC-RPE do not differ much in gene expression. Our data further showed that pigmented hESC-RPE has a significant lower expression than human endogenous RPE in the visual cycle and oxidative stress pathways. In contrast, we observed a significantly higher expression of pathways related to the process adhesion-to-polarity model that is typical of developing epithelial cells. We conclude that, in vitro, the first appearance of pigmentation hallmarks differentiated RPE. However, further increase in pigmentation does not result in much significant gene expression changes and does not add important RPE functionalities. Consequently, our results suggest that the time span for obtaining differentiated hESC-RPE cells, that are suitable for transplantation, may be greatly reduced. The online version of this article (doi:10.1007/s12015-017-9754-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Janssen S;Laermans J;Iwakura H;Tack J;Depoortere I
通讯作者：
Depoortere I
DOI：
10.1089/clo.2006.8.189
发表时间：
2006-09-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Lund, Raymond D.;Wang, Shaomei;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
3.4
作者：
Liang, FQ;Green, L;Godley, BF
通讯作者：
Godley, BF
影响因子：
4.7
作者：
Rastmanesh, Reza
通讯作者：
Rastmanesh, Reza
影响因子：
5.9
作者：
Plaza Reyes A;Petrus-Reurer S;Antonsson L;Stenfelt S;Bartuma H;Panula S;Mader T;Douagi I;André H;Hovatta O;Lanner F;Kvanta A
通讯作者：
Kvanta A