Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD.
Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD.
复制标题
DOI：
10.1111/gtc.12127
复制
发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Seko Y;Azuma N;Ishii T;Komuta Y;Miyamoto K;Miyagawa Y;Kaneda M;Umezawa A
通过转录因子的过度表达来重定向体细胞的分化是再生医学、阐明发病机制和开发新疗法的一种有前途的方法。我们之前定义了一种转录因子组合，即CRX、RAX和NEUROD，可以从人类虹膜细胞生成感光感光细胞。在这里，我们证明人真皮成纤维细胞通过与人虹膜细胞相同的转录因子组合分化为感光细胞。在所测试的所有三种人真皮成纤维细胞株中，CRX、RAX 和 NEUROD 基因组合的转导上调了光感受器特异性基因、恢复蛋白、蓝视蛋白和 PDE6C 的表达。额外的 OTX2 基因转导增加了光感受器特异性基因蓝视蛋白、恢复蛋白、S-抗原、CNGB3 和 PDE6C 的上调。微阵列分析的全局基因表达数据进一步表明，诱导感光细胞中感光相关功能基因显着增加。功能分析，即膜片钳记录，清楚地揭示了成纤维细胞诱导的感光细胞对光做出反应。 NRL 基因和 NR2E3 基因在诱导感光细胞中内源性上调，这意味着外源 CRX、RAX、OTX2 和 NEUROD（而非 NRL）足以产生视杆细胞。
Redirecting differentiation of somatic cells by over-expression of transcription factors is a promising approach for regenerative medicine, elucidation of pathogenesis and development of new therapies. We have previously defined a transcription factor combination, that is, CRX, RAX and NEUROD, that can generate photosensitive photoreceptor cells from human iris cells. Here, we show that human dermal fibroblasts are differentiated to photoreceptor cells by the same transcription factor combination as human iris cells. Transduction of a combination of the CRX, RAX and NEUROD genes up-regulated expression of the photoreceptor-specific genes, recoverin, blue opsin and PDE6C, in all three strains of human dermal fibroblasts that were tested. Additional OTX2 gene transduction increased up-regulation of the photoreceptor-specific genes blue opsin, recoverin, S-antigen, CNGB3 and PDE6C. Global gene expression data by microarray analysis further showed that photoreceptor-related functional genes were significantly increased in induced photoreceptor cells. Functional analysis, that is, patch-clamp recordings, clearly revealed that induced photoreceptor cells from fibroblasts responded to light. Both the NRL gene and the NR2E3 gene were endogenously up-regulated in induced photoreceptor cells, implying that exogenous CRX, RAX, OTX2 and NEUROD, but not NRL, are sufficient to generate rod photoreceptor cells.
登录
查看更多内容
通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
30.8
作者：
Mears, AJ;Kondo, M;Swaroop, A
通讯作者：
Swaroop, A
影响因子：
64.5
作者：
Furukawa, T;Morrow, EM;Cepko, CL
通讯作者：
Cepko, CL
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
64.8
作者：
Mathers, PH;Grinberg, A;Jamrich, M
通讯作者：
Jamrich, M