Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells
Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells
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DOI：
10.1002/stem.1470
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发表时间：
2013-10-01
期刊：
影响因子：
5.2
通讯作者：
van der Kooy, Derek
中科院分区：
文献类型：
--
作者：
Balenci, Laurent;Wonders, Carl;van der Kooy, Derek
成年小鼠和人眼视网膜边缘睫状上皮内的罕见视网膜干细胞（RSCs）可以在不存在生长因子的情况下在体外分裂以产生克隆的自我更新球体，其可以产生所有视网膜细胞类型。由于在成年哺乳动物眼睛中没有原位观察到再生特性，我们试图确定参与内源性RSC抑制的因素。我们发现成人透镜和角膜分泌的因子在体外阻断成人RSCs的增殖。骨形态发生蛋白（BMP）2、BMP 4和分泌型卷曲相关蛋白2被鉴定为对RSC的抗增殖作用的主要效应物。由于在体外对小鼠和人RSC都观察到类似的诱导静止，因此体内靶向这些分子可以直接在盲人眼中原位重新激活RSC。干细胞2013;31：2218-2230
Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind. Stem Cells 2013;31:2218-2230