MicroRNA-9 协调人胚胎干细胞源性神经祖细胞的增殖和迁移。
MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.
机构信息
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA.
Center for Cerebrovascular Research, Departments of Anesthesia and Perioperative Care and Neurology and Neurosurgery, University of California, San Francisco, CA 94110, USA.
出版信息
Cell Stem Cell. 2010 Apr 2;6(4):323-335. doi: 10.1016/j.stem.2010.02.015.
Human pluripotent stem cells offer promise for use in cell-based therapies for brain injury and diseases. However, their cellular behavior is poorly understood. Here we show that the expression of the brain-specific microRNA-9 (miR-9) is turned on in human neural progenitor cells (hNPCs) derived from human embryonic stem cells. Loss of miR-9 suppressed proliferation but promoted migration of hNPCs cultured in vitro. hNPCs without miR-9 activity also showed enhanced migration when transplanted into mouse embryonic brains or adult brains of a mouse model of stroke. These effects were not due to precocious differentiation of hNPCs. One of the key targets directly regulated by miR-9 encodes stathmin, which increases microtubule instability and whose expression in hNPCs correlates inversely with that of miR-9. Partial inhibition of stathmin activity suppressed the effects of miR-9 loss on proliferation and migration of human or embryonic rat neural progenitors. These results identify miR-9 as a novel regulator that coordinates the proliferation and migration of hNPCs.
人类多能干细胞为脑损伤和疾病的细胞治疗提供了希望。然而，它们的细胞行为还知之甚少。在这里，我们表明，在源自人类胚胎干细胞的人神经祖细胞（hNPC）中，脑特异性 microRNA-9（miR-9）的表达被激活。miR-9 的缺失抑制了体外培养的 hNPC 的增殖，但促进了其迁移。当没有 miR-9 活性的 hNPC 被移植到小鼠胚胎大脑或中风小鼠模型的成年大脑中时，它们的迁移也得到了增强。这些影响不是由于 hNPC 的早熟分化引起的。miR-9 直接调控的一个关键靶标编码 stathmin，它增加了微管的不稳定性，并且其在 hNPC 中的表达与 miR-9 呈负相关。stathmin 活性的部分抑制抑制了 miR-9 缺失对人或胚胎大鼠神经祖细胞增殖和迁移的影响。这些结果表明 miR-9 是一种新的调节因子，它协调 hNPC 的增殖和迁移。
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