Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro.
Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro.
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DOI：
10.1242/dev.155838
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
O'Connor MD
中科院分区：
文献类型：
--
作者：
Murphy P;Kabir MH;Srivastava T;Mason ME;Dewi CU;Lim S;Yang A;Djordjevic D;Killingsworth MC;Ho JWK;Harman DG;O'Connor MD
白内障通过损害眼晶状体将光线聚焦到视网膜的能力而导致视力丧失和失明。已经确定了多种白内障危险因素，包括药物治疗、年龄、吸烟和糖尿病。然而，导致这些不同形式白内障的分子事件尚不明确，而且 20 世纪 60 年代现代白内障手术的出现实际上消除了对人类晶状体进行研究的机会。在这里，我们展示了利用从分化的多能干细胞中纯化的球形人类晶状体上皮细胞大规模生产光聚焦人类微晶状体。纯化的晶状体细胞和微晶状体表现出与人类晶状体细胞和晶状体相似的形态、细胞排列、mRNA表达和蛋白质表达。将微透镜暴露于囊性纤维化药物 Vx-770 中会降低微透镜的透明度和聚焦能力。这些人体微晶状体为定义白内障危险因素引起的分子疾病机制、抗白内障药物筛选和临床相关毒性测定提供了强大的大规模平台。 使用人类多能干细胞，描述了用于大规模生产纯化的人类晶状体上皮细胞以及随后大规模生成临床相关的光聚焦微晶状体的稳健且可靠的方法。
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. Using human pluripotent stem cells, robust and reliable methods are described for large-scale production of purified human lens epithelial cells, and for subsequent large-scale generation of clinically relevant, light-focusing micro-lenses.
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1126/science.aac9145
发表时间：
2015-11-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Makley LN;McMenimen KA;DeVree BT;Goldman JW;McGlasson BN;Rajagopal P;Dunyak BM;McQuade TJ;Thompson AD;Sunahara R;Klevit RE;Andley UP;Gestwicki JE
通讯作者：
Gestwicki JE
影响因子：
5.6
作者：
Li, Dan;Qiu, Xiaodi;Lu, Yi
通讯作者：
Lu, Yi
影响因子：
3.1
作者：
Talamo Guevara M;McColley SA
通讯作者：
McColley SA
DOI：
10.2147/ijnrd.s85733
发表时间：
2015-01-01
影响因子：
2
作者：
Chen, Wenbiao;Huang, Jianrong;Dai, Yong
通讯作者：
Dai, Yong