Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

被引:11
作者
Balenci, Laurent [1 ]
Wonders, Carl [1 ]
Coles, Brenda L. K. [1 ]
Clarke, Laura [1 ]
van der Kooy, Derek [1 ]
机构
[1] Univ Toronto, Dept Mol Genet, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada
基金
加拿大健康研究院;
关键词
Bone morphogenetic proteins; Adult retinal stem cells; Secreted Frizzled Related Protein 2; Lens; Quiescence; Cornea; CILIARY EPITHELIUM; PROGENITOR CELLS; MULTIPOTENT PRECURSORS; PARS-PLANA; MARGIN; GROWTH; DIFFERENTIATION; NEURONS; PROLIFERATION; ACTIVATION;
D O I
10.1002/stem.1470
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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
引用
收藏
页码:2218 / 2230
页数:13
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