Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation

Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation
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DOI:
10.1016/j.brainres.2006.03.093
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发表时间:
2006-06-06
期刊:
影响因子:
2.9
通讯作者:
Sueishi, Katsuo
Sueishi, Katsuo
中科院分区:
医学3区
文献类型:
--
作者:
Kohno, Ri-ichiro;Ikeda, Yasuhiro;Sueishi, Katsuo

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众所周知,中枢神经系统(CNS)的神经干/祖细胞可以增殖以形成对巢蛋白(神经祖细胞的中间丝)呈阳性的神经球(CNS-神经球)。视网膜干细胞/祖细胞特性也从眼睛的睫状体(CB)中分离,其中,如在CNS中,这样的干细胞/祖细胞也形成球体,并且已经被认为仅通过其增殖的扩增而扩增,甚至从单细胞水平(称为来自睫状缘的色素细胞球体:PCM-球体)。我们在这里发现了一个新的和独特的过程的CB细胞衍生的球体(CB球)的增长,这是不同的机制CNS和PCM球的扩张,这个新的过程是一个细胞增殖独立的掺入的邻居球和细胞培养在高密度(200个细胞/μ l)。CB球中的大多数细胞由巢蛋白阴性的上皮样细胞组成,并在其通过高密度培养扩增的过程中开始表达巢蛋白。CNS-神经球的生长对细胞周期抑制剂敏感,而CB-球的生长不受细胞增殖的严重影响;相反,球通过将其他CB-球和巢蛋白阴性贴壁细胞结合而生长,后者开始表达巢蛋白并在被结合后失去上皮标记物的表达。这些结果表明,CB球不形成的神经祖细胞的积累,而是通过一个重编程系统从上皮样细胞的神经分化,一个明显不同的机制,从球体形成视网膜干细胞/祖细胞群体的单细胞扩增。(c)2006 Elsevier B. V.保留所有权利。
It is well known that neural stem/progenitor cells of the central nervous system (CNS) can proliferate to form neurospheres (CNS-neurospheres) that are positive for nestin, an intermediate filament for neural progenitors. Retinal stem/progenitor properties were also isolated from the ciliary body (CB) of the eye where, as in the CNS, such stem/progenitors also form spheres and have been considered to expand only via expansion by their proliferation even from the single-cell level (called spheres of pigment cells from the ciliary margin: PCM-spheres). We here found a new and distinct process underlying the growth of CB cell-derived spheres (CB-spheres) that is unlike the mechanism of CNS- and PCM-sphere expansion; this new process is a cell proliferation-independent incorporation of neighbor spheres and cells cultured at high density (200 cells/mu l). The majority of cells in CB-spheres consisted of nestin-negative epithelia-like cells and started to express nestin during the course of their expansion by high-density cultivation. The growth of CNS-neurospheres was sensitive to a cell-cycle inhibitor, whereas the growth of CB-spheres was not seriously affected by cell proliferation; rather, the spheres grew by incorporating other CB-spheres and nestin-negative adherent cells, the latter of which started to express nestin and lost the expression of epithelial markers after being incorporated. These results indicate that CB-spheres do not form by the accumulation of neural progenitors but rather by a reprogramming system from epithelia-like cells for neural differentiation, a clearly distinct mechanism from sphere formation by single-cell expansion of retinal stem/progenitor populations. (c) 2006 Elsevier B.V. All rights reserved.