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中外学者合作可将皮肤干细胞诱导分化为角膜缘干细胞

摘要 : 日前,中山大学中山眼科中心研究团队与美国加州大学圣地亚哥分校研究团队联手,证实了调控角膜缘干细胞分化的关键因子WNT7A和PAX6在角膜谱系专向分化中起着重要的作用,首次将皮肤干细胞诱导分化为角膜缘干细胞,并成功修复角膜功能,为治疗角膜疾病指出了一条新策略。7月2日,相关研究在《自然》杂志在线发表。这也是中国大陆眼科学者作为主要作者之一首次在《自然》发表研究成果。

 日前,中山大学中山眼科中心研究团队与美国加州大学圣地亚哥分校研究团队联手,证实了调控角膜缘干细胞分化的关键因子WNT7A和PAX6在角膜谱系专向分化中起着重要的作用,首次将皮肤干细胞诱导分化为角膜缘干细胞,并成功修复角膜功能,为治疗角膜疾病指出了一条新策略。7月2日,相关研究在《自然》杂志在线发表。这也是中国大陆眼科学者作为主要作者之一首次在《自然》发表研究成果。

该项目负责人表示,一直以来,角膜缘干细胞移植受限于供体来源不足及异体移植排斥反应。而这份发表在《自然》杂志上的研究成果的意义在于,可快速且廉价地将皮肤上皮干细胞或其他的细胞类型分化、扩增出足量的角膜缘干细胞,从而为修复和再生角膜表面、治疗角膜缘干细胞缺陷提供了一个潜在资源。这对于治疗临床上角膜缘干细胞功能受损导致的重大疾病及修复近视眼术后上皮损伤展现了广阔的应用前景。

上述成果是中山大学眼科学国家重点实验室积极发挥“开放、流动、联合、竞争”运行机制的作用,在国家重点实验室这一平台上开展合作研究和联合攻关的产物。成果的主要负责人包括美国加州大学圣地亚哥分校人类基因组医学研究所所长张康教授和中山大学中山眼科中心主任、眼科医院院长刘奕志等。

原文摘要:

WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis

Hong Ouyang, Yuanchao Xue, Ying Lin, Xiaohui Zhang, Lei Xi, Sherrina Patel, Huimin Cai,Jing Luo, Meixia Zhang, Ming Zhang, Yang Yang, Gen Li, Hairi Li, Wei Jiang, Emily Yeh,Jonathan Lin, Michelle Pei, Jin Zhu, Guiqun Cao, Liangfang Zhang, Benjamin Yu,Shaochen Chen, Xiang-Dong Fu, Yizhi Liu & Kang Zhang

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.

来源: 中国科学报 浏览次数:126

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