Potency and Fate Specification in CNS Stem Cell Populations In Vitro
Potency and Fate Specification in CNS Stem Cell Populations In Vitro
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DOI：
10.1016/j.stem.2008.09.012
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发表时间：
2008-12-04
期刊：
影响因子：
23.9
通讯作者：
Mckay, Ronald D. G.
中科院分区：
文献类型：
--
作者：
Ravin, Rea;Hoeppner, Daniel J.;Mckay, Ronald D. G.
为了实现干细胞生物学的前景，重要的是要确定细胞发育潜力受到限制的确切时间。为了实现这一目标，我们开发了一种实时成像系统，该系统捕获命运的转变，在体外从单个CNS干细胞产生神经元、星形胶质细胞和少突胶质细胞。在碱性成纤维细胞生长因子的存在下，三能细胞通常通过双能中间细胞类型产生特定的祖细胞。令人惊讶的是，三能状态在每次传代时都被重置。细胞因子CNTF被认为指导多能细胞向星形胶质细胞的命运。我们证明，CNTF既指导星形胶质细胞从三能细胞，绕过两个正常的双能中间体，后来促进特定的星形胶质细胞祖细胞的扩增。这些结果显示了离散的细胞类型是如何从多能细胞中产生的，并为未来的研究提供了强有力的基础，以确定命运特化的分子基础。
To realize the promise of stem cell biology, it is important to identify the precise time in the history of the cell when developmental potential is restricted. To achieve this goal, we developed a real-time imaging system that captures the transitions in fate, generating neurons, astrocytes, and oligodendrocytes from single CNS stem cells in vitro. In the presence of bFGF, tripotent cells normally produce specified progenitors through a bipotent intermediate cell type. Surprisingly, the tripotent state is reset at each passage. The cytokine CNTF is thought to instruct multipotent cells to an astrocytic fate. We demonstrate that CNTF both directs astrogliogenesis from tripotent cells, bypassing two of the three normal bipotent intermediates, and later promotes the expansion of specified astrocytic progenitors. These results show how discrete cell types emerge from a multipotent cell and provide a strong basis for future studies to determine the molecular basis of fate specification.