Oligodendrocyte progenitors reversibly exit the cell cycle and give rise to astrocytes in response to interferon-γ.
Oligodendrocyte progenitors reversibly exit the cell cycle and give rise to astrocytes in response to interferon-γ.
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DOI：
10.1523/jneurosci.5905-10.2011
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发表时间：
2011-04-20
期刊：
影响因子：
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通讯作者：
Mayer-Pröschel M
中科院分区：
文献类型：
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作者：
Tanner DC;Cherry JD;Mayer-Pröschel M
Oligodendrocyte – type-2 astrocyte progenitor cells (O-2A/OPCs) populate the CNS and generate oligodendrocytes and astrocytes in vitro and in vivo. Understanding how O-2A/OPCs respond to their environment is crucial to understanding how these cells function in the CNS and how to best promote their therapeutic proliferation and differentiation. We show that IFN-γ was not toxic to highly purified perinatal or adult rat O-2A/OPCs. IFN-γ treatment led to downregulation of PDGFR-α and Ki-67 and decreased self-renewal in clonal populations. IFN-γ also significantly increased the proportion of cells in the G0/G1 phase of the cell cycle, decreased BrdU incorporation, and led to increased expression of the cell cycle inhibitors Rb and p27kip1. While p27kip1 expression was not necessary for IFN-γ – mediated quiescence, its upstream regulator IRF-1 was required. The quiescent state of O-2A/OPCs caused by INF-γ was reversible as the withdrawal of IFN-γ allowed O-2A/OPCs to appropriately respond to both proliferation and differentiation signals. Differentiation into oligodendrocytes induced by either thyroid hormone or CNTF was also abrogated by IFN-γ. This inhibition was specific to the oligodendrocyte pathway, as O-2A/OPC differentiation into astrocytes was not inhibited. IFN-γ alone also led to the generation of GFAP positive astrocytes in a subset of O-2A/OPCs. Taken together these results demonstrate a reversible inhibitory effect of IFN-γ on O-2A/OPC proliferation with a concomitant generation of astrocytes. We propose that neuroinflammation involving increased IFN-γ can reduce progenitor numbers and inhibit differentiation, which has significant clinical relevance for injury repair, but may also contribute to the generation of astrocytes.
