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WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis

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作者：
Ouyang, H[a,b] ; Xue, Y[c] ; Lin, Y[a,b] ; Zhang, X[b,j] ; Xi, L[a,b] ; Patel, S[b] ; Cai, H[d,e] ; Luo, J[b] ; Zhang, M[d] ; Zhang, M[d] ; Yang, Y[b,k] ; Li, G[d] ; Li, H[c] ; Jiang, W[d] ; Yeh, E[b] ; Lin, J[b] ; Pei, M[b] ; Zhu, J[b] ; Cao, G[d] ; Zhang, L[b,f] ; Yu, B[g,h] ; Chen, S[b,f] ; Fu, X.-D[b,c,h] ; Liu, Y[a] ; Zhang, K[a,b,d,h,i] ;
机构： [a]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [b]Department of Ophthalmology, Biomaterial and Tissue Engineering Center, University of California San Diego, San Diego, CA 92093, United States [c]Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA 92093, United States [d]Molecular Medicine Research Center, West China Hospital, Sichuan University, Sichuan 610041, China [e]Guangzhou KangRui Biological Pharmaceutical Technology Company Ltd., Guangzhou 510005, China [f]Department of Nanoengineering, University of California San Diego, San Diego, CA 92093, United States [g]Department of Medicine, University of California San Diego, San Diego, CA 92093, United States [h]Institute for Genomic Medicine, University of California San Diego, San Diego, CA 92093, United States [i]Veterans Administration Healthcare System, San Diego, CA 92093, United States [j]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730, China [k]Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang 110004, China
出处：
DOI： 10.1038/nature13465
ISSN：

摘要：
The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium - which turns cornea into a non-transparent, keratinized skin-like epithelium - causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases. © 2014 Macmillan Publishers Limited. All rights reserved.

基金：
Acknowledgements This study is supported in part by the 973 program (2013CB967504 and 2014CB964900), Project of Fundamental Research Funds (no.2012KF03), State Key laboratory of Ophthalmology, NIH (GM049369), KACST-UCSD Center of Excellence in Nanomedicine, NIH Director’s Transformative RO1 Program (R01 EY021374) and CIRM.
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出版当年[2014]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
第一作者：
第一作者机构： [a]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [b]Department of Ophthalmology, Biomaterial and Tissue Engineering Center, University of California San Diego, San Diego, CA 92093, United States
通讯作者：
通讯机构： [a]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [b]Department of Ophthalmology, Biomaterial and Tissue Engineering Center, University of California San Diego, San Diego, CA 92093, United States [c]Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, CA 92093, United States [d]Molecular Medicine Research Center, West China Hospital, Sichuan University, Sichuan 610041, China [h]Institute for Genomic Medicine, University of California San Diego, San Diego, CA 92093, United States [i]Veterans Administration Healthcare System, San Diego, CA 92093, United States
推荐引用方式(GB/T 7714)：
Ouyang H,Xue Y,Lin Y,et al.WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis[J].Nature.2014,511(7509):358-61.doi:10.1038/nature13465.
APA：
Ouyang, H,Xue, Y,Lin, Y,Zhang, X,Xi, L...&Zhang, K.(2014).WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.Nature,511,(7509)
MLA：
Ouyang, H,et al."WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis".Nature 511..7509(2014):358-61

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