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

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• 作者：Ri-ichiro Kohno ; Yasuhiro Ikeda ; Yoshikazu Yonemitsu ; Toshio Hisatomi ; Masahiro Yamaguchi ; Masanori Miyazaki ; Hiroko Takeshita ; Tatsuro Ishibashi and Katsuo Sueishi
• 关键词：Stem/progenitor cell ; Neurosphere ; Nestin ; Ciliary body ; Reprogramming
• 刊名：Brain Research
• 出版年：2006
• 出版时间：6 June 2006
• 年：2006
• 卷：1093
• 期：1
• 页码：54-70
• 全文大小：1232 K

文摘

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/μl). 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.