Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells
Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells
复制标题
DOI：
10.1634/stemcells.2007-1067
复制
发表时间：
2008-05-01
期刊：
影响因子：
5.2
通讯作者：
Kinoshita, Shigeru
中科院分区：
文献类型：
--
作者：
Nakamura, Takahiro;Ohtsuka, Toshiyuki;Kinoshita, Shigeru
Hes 1是Notch信号转导的主要靶基因，在许多发育系统中调节各种细胞类型的命运和分化。为了获得对Hes 1在角膜组织中的作用的新见解，我们进行了功能获得和功能丧失研究。我们发现，角膜发育严重干扰Hes 1基因敲除小鼠。Hes 1缺失的角膜表现出异常的交界特化、细胞分化和较低的细胞增殖能力。值得注意的是，Hes 1主要在角膜上皮干/祖细胞中表达，而在分化的角膜上皮细胞中未检测到。Hes 1的表达与角膜上皮干/祖细胞在体内的增殖活性密切相关。此外，强制Hes 1表达抑制角膜上皮干/祖细胞的分化并维持这些细胞的未分化状态。我们的数据提供了第一个证据表明，Hes 1调节角膜发育和角膜上皮干/祖细胞的稳态功能。
Hes1, a major target gene in Notch signaling, regulates the fate and differentiation of various cell types in many developmental systems. To gain a novel insight into the role of Hes1 in corneal tissue, we performed gain-of-function and loss-of-function studies. We show that corneal development was severely disturbed in Hes1-null mice. Hes1-null corneas manifested abnormal junctional specialization, cell differentiation, and less cell proliferation ability. Worthy of note, Hes1 is expressed mainly in the corneal epithelial stem/progenitor cells and is not detected in the differentiated corneal epithelial cells. Expression of Hes1 is closely linked with corneal epithelial stem/progenitor cell proliferation activity in vivo. Moreover, forced Hes1 expression inhibits the differentiation of corneal epithelial stem/progenitor cells and maintains these cells' undifferentiated state. Our data provide the first evidence that Hes1 regulates corneal development and the homeostatic function of corneal epithelial stem/progenitor cells.