80cb39dbb6fd5266d4c7defaaa18972bd507366b

国马萨诸塞眼耳科研究所的研究团队利用一种名为“ABCB5”的分子,他们发现了促进人类角膜组织再生、让失明者恢复视力的方法。研究人员相信,这一里程碑式的突破可帮助“修正”导致失明的主要原因。

                                                                                                                                                                           -2014年7月2日《自然》

中文翻译


【题目】ABCB5是一个对于角膜发育和修复必需的角膜缘干细胞基因

【译文】 角膜缘干细胞(LSCs)能够维持角膜上皮的内稳态和再生,而LSC缺陷是一个造成世界范围性失明的主要原因。通常移植是对于LSC缺陷症患者唯一的治疗选择。然后,尽管移植的成功主要取决于LSC细胞的多少,但是潜在的决定LSC丰度的基因至今还没有确定。这篇文章中我们展示了ATP-结合盒蛋白亚家族B的5号成员(ABCB5)作为LSCs的标记,对于维持LSC、角膜的发育和修复存在着至关重要的作用。此外,我们的研究还表明分离出的人或者鼠科ABCB5阳性标记的LSCs,可以使得异源基因或同源基因移植模型中LSC缺陷小鼠通过移植而完全恢复角膜的能力。ABCB5可以优先在小鼠标记滞留的LSCs细胞和人的p63α-阳性LSC细胞中表达。与这些发现一致的是,在LSC缺陷病人中ABCB5-阳性标记的LSC的细胞是很少的。Abcb5敲除后的小鼠,由于增殖和细胞凋亡作用的增加,Abcb5功能的丧失将会导致静态LSC细胞的损耗,从而引起缺陷的角膜分化和伤口愈合。我们的研究通过基因敲除模型、LSC追踪和移植模型,以及人类活检标本的表型和功能的分析等提供确凿的证据证明ABCB5能够识别哺乳类LSCs。识别和特异的分离(分子水平上证实)的LSCs对于角膜的发育和修复具有不可或缺的作用,并且对于治疗角膜疾病有着非常重要的意义,特别是LSC缺乏的角膜盲。

英文原稿


[Title]: ABCB5 is a limbal stemcell gene required for corneal development and repair

[Authors]Bruce R. Ksander*, Paraskevi E. Kolovou*, Brian J.Wilson, Karim R. Saab, Qin Guo, Jie Ma, Sean P. McGuire, Meredith S. Gregory, William J. B. Vincent1, Victor L. Perez, Fernando Cruz-Guilloty, Winston W. Y. Kao, Mindy K. Call Budd A. Tucker, Qian Zhan, George F. Murphy, Kira L. Lathrop, Clemens Alt, Luke J. Mortensen, Charles P. Lin, James D. Zieske1, Markus H. Frank* & Natasha Y. Frank*

[Abstract]: Corneal epithelial homeostasis and regeneration are sustained by limbal stem cells (LSCs), and LSC deficiency is a major cause of blindness worldwide. Transplantation is often the only therapeutic option available to patients with LSC deficiency. However,while transplant success depends foremost on LSC frequency within grafts, a gene allowing for prospective LSC enrichment has not been identified so far. Here we show that ATP-binding cassette, sub-family B, member 5 (ABCB5)marks LSCs and is required for LSC maintenance, corneal development and repair. Furthermore, we demonstrate that prospectively isolated human or murine ABCB5-positive LSCs possess the exclusive capacity to fully restore the cornea upon grafting to LSC deficient mice in xenogeneic or syngeneic transplantation models. ABCB5 is preferentially expressed on label-retaining LSCs in mice and p63a-positive LSCs in humans. Consistent with these findings, ABCB5-positive LSC frequency is reduced in LSC-deficient patients. Abcb5 loss of function in Abcb5 knockout mice causes depletion of quiescent LSCs due to enhanced proliferation and apoptosis, and results in defective corneal differentiation and wound healing. Our results from gene knockout studies, LSC tracing and transplantation models, as well as phenotypic and functional analyses of human biopsy specimens, provide converging lines of evidence that ABCB5 identifies mammalian LSCs. Identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency.

原文地址

http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature13426.pdf

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201407/1982/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


五 − = 4


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息