Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD.
Derivation of human differential photoreceptor-like cells from the iris by defined combinations of CRX, RX and NEUROD.
复制标题
DOI：
10.1371/journal.pone.0035611
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Seko Y;Azuma N;Kaneda M;Nakatani K;Miyagawa Y;Noshiro Y;Kurokawa R;Okano H;Umezawa A
已经为β细胞、心肌细胞和神经元提供了通过确定的转录因子直接分化的实例。在人类视觉系统中，视网膜上有四种光感受器。神经视网膜和虹膜色素上皮（IPE）有着共同的发育起源，这使我们能够测试人类虹膜细胞是否可以分化为视网膜神经元。我们在这里定义的转录因子组合，可以决定人类感光细胞的命运。诱导的感光细胞中视紫红质、蓝色视蛋白和绿色/红色视蛋白的表达依赖于转录因子的组合：CRX和NEUROD的组合诱导视紫红质和蓝色视蛋白，但不诱导绿色视蛋白; CRX和RX的组合诱导蓝色视蛋白和绿色/红色视蛋白，但不诱导视紫红质。光转导相关基因以及视蛋白基因在这些细胞中表达上调。功能分析;即膜片钳记录，清楚地揭示了由CRX、RX和NEUROD诱导产生的感光细胞对光有反应。反应是内向电流，而不是典型的外向电流。这些数据表明，光敏感光细胞可以通过转录因子的组合产生。CRX和RX的组合产生未成熟的光感受器：额外的NEUROD促进成熟。这些发现大大有助于最终以细胞为基础的治疗视网膜退行性疾病的重大进展。
Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases.
登录
查看更多内容
DOI：
10.1073/pnas.0401596101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Coles, BLK;Angénieux, B;van der Kooy, D
通讯作者：
van der Kooy, D
影响因子：
30.8
作者：
Mears, AJ;Kondo, M;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
5.3
作者：
Hartwick, Andrew T. E.;Bramley, Jayne R.;Pickard, Gary E.
通讯作者：
Pickard, Gary E.
影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
Reh, TA
DOI：
10.1073/pnas.0705878104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Manavathi, Bramanandam;Peng, Shaohua;Kumar, Rakesh
通讯作者：
Kumar, Rakesh