Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes.

Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes.
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DOI:
10.1016/j.celrep.2013.06.021
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发表时间:
2013-09-12
期刊:
影响因子:
8.8
通讯作者:
Henderson CE
Henderson CE
中科院分区:
生物学1区
文献类型:
--
作者:
Roybon L;Lamas NJ;Garcia AD;Yang EJ;Sattler R;Lewis VJ;Kim YA;Kachel CA;Rothstein JD;Przedborski S;Wichterle H;Henderson CE

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星形胶质细胞与人类干细胞的分化对于分析其在正常大脑功能和疾病中的作用具有巨大的潜力,但现有的方案仅产生不成熟的星形胶质细胞。利用早期神经化,我们从小鼠或人胚胎 (ESC) 或诱导多能 (hiPSC) 干细胞中高效生成脊髓星形胶质细胞。值得注意的是,根据标记物表达和功能分析判断,短暂暴露于 FGF1 或 FGF2 足以选择性地将这些星形胶质细胞引导至成熟的静止表型。相比之下,TNFα 和 IL-1β(而非 FGF)诱导反应表型的多种元素,但不影响成熟。这些表型明确的、可扩展的脊髓星形胶质细胞群体对于研究正常星形胶质细胞功能和体外模拟人类病理过程都很重要。
Differentiation of astrocytes from human stem cells has significant potential for analyzing their role in normal brain function and disease, but existing protocols generate only immature astrocytes. Using early neuralization, we generated spinal cord astrocytes from mouse or human embryonic (ESCs) or induced pluripotent (hiPSCs) stem cells with high efficiency. Remarkably, short exposure to FGF1 or FGF2 was sufficient to direct these astrocytes selectively toward a mature quiescent phenotype, as judged both by marker expression and functional analysis. In contrast, TNFα and IL-1β but not FGFs, induced multiple elements of a reactive phenotype but did not affect maturation. These phenotypically defined, scalable populations of spinal cord astrocytes will be important both for studying normal astrocyte function and for modeling human pathological processes in vitro.
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