Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity
Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity
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DOI：
10.1016/s0896-6273(00)00083-0
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发表时间：
2000-10-01
期刊：
影响因子：
16.2
通讯作者：
Sasai, Y
中科院分区：
文献类型：
--
作者：
Kawasaki, H;Mizuseki, K;Sasai, Y
我们已经确定了一种基质细胞衍生的诱导活性(SDIA)，它可以促进小鼠ES细胞的神经分化。SDIA聚集在PA6基质细胞的表面，在无血清条件下诱导共培养的ES细胞高效分化，而不使用维甲酸或类胚体。BMP4在非洲爪哇中作为一种抗神经化的形态原，抑制SDIA诱导的神经化，促进表皮分化。SDIA处理的ES细胞中有很高比例的酪氨酸羟基酶阳性神经元产生多巴胺。移植后，SDIA诱导的多巴胺能神经元整合到小鼠纹状体中，并保持酪氨酸羟化酶表达阳性。SDIA的神经诱导为基础神经科学研究和治疗应用提供了新的强有力的工具。
We have identified a stromal cell–derived inducing activity (SDIA) that promotes neural differentiation of mouse ES cells. SDIA accumulates on the surface of PA6 stromal cells and induces efficient neuronal differentiation of cocultured ES cells in serum-free conditions without use of either retinoic acid or embryoid bodies. BMP4, which acts as an antineuralizing morphogen inXenopus, suppresses SDIA-induced neuralization and promotes epidermal differentiation. A high proportion of tyrosine hydroxylase-positive neurons producing dopamine are obtained from SDIA-treated ES cells. When transplanted, SDIA-induced dopaminergic neurons integrate into the mouse striatum and remain positive for tyrosine hydroxylase expression. Neural induction by SDIA provides a new powerful tool for both basic neuroscience research and therapeutic applications.