期刊
CORNEA
卷 38, 期 -, 页码 S34-S41出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ICO.0000000000002074
关键词
direct reprogramming; corneal epithelial cell; PAX6; OVOL2; KLF4; transcription factor; reprogramming; transdifferentiation
资金
- Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical
- Japanese Society for the Promotion of Science (JSPS) (KAKENHI) [16K20324, 18K16390]
- Grants-in-Aid for Scientific Research [16K20324, 18K16390] Funding Source: KAKEN
In its early stages, an embryo polarizes to form cell subpopulations that subsequently produce specific organ cell types. These cell subpopulations are defined by transcription factors (TFs) that activate or repress specific genes. Although an embryo comprises thousands of TFs, surprisingly few are needed to determine the fate of a given cell. The ectoderm divides into the neuroectoderm and surface ectoderm, the latter of which gives rise to epidermal keratinocytes and corneal epithelial cells (CECs). Meanwhile, neuroectoderm cells give rise to other parts of the eye such as the corneal endothelium and retina. To investigate the regulatory role of TFs in CECs, we overexpressed the core TFs (PAX6, OVOL2, and KLF4) in human fibroblasts and found that the cells adopted a CEC-like quality. OVOL2 overexpression was even able to directly induce cells with a neuroectoderm fate toward a surface ectoderm fate, designated direct reprogramming. Conversely, suppression of OVOL2 or PAX6 expression induced CECs to show qualities consistent with neural lineage cells or epidermal keratinocytes, respectively. This suggests that these core TFs can maintain the CEC phenotype through reciprocal gene regulation. Direct reprogramming has important implications for cell therapies. The potential benefits of cells derived by direct reprogramming compared with induced pluripotent stem cells include the fact that it requires less time than reprogramming a cell back to the pluripotent state and then to another cell type. Further understanding of the reciprocally repressive mechanism of action for core TFs could lead to alternative treatments for regenerative medicine not requiring cell transplantation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据