MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.
MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors.
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DOI：
10.1016/j.stem.2010.02.015
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发表时间：
2010-04-02
期刊：
影响因子：
23.9
通讯作者：
Gao FB
中科院分区：
文献类型：
--
作者：
Delaloy C;Liu L;Lee JA;Su H;Shen F;Yang GY;Young WL;Ivey KN;Gao FB
人类多能干细胞有望用于基于细胞的脑损伤和疾病治疗。然而，人们对它们的细胞行为知之甚少。在这里，我们发现脑特异性microRNA-9 （miR-9）的表达在人类胚胎干细胞衍生的人类神经祖细胞（hNPCs）中被开启。miR-9的缺失抑制了体外培养的hNPCs的增殖，但促进了其迁移。没有miR-9活性的hNPCs在移植到小鼠胚胎脑或中风小鼠模型的成年脑时也表现出增强的迁移。这些影响不是由于hNPCs的早熟分化。miR-9直接调控的关键靶点之一编码stathmin，其增加微管不稳定性，其在hNPCs中的表达与miR-9呈负相关。部分抑制安定素活性可抑制miR-9缺失对人或胚胎大鼠神经祖细胞增殖和迁移的影响。这些结果确定miR-9是一种协调hNPCs增殖和迁移的新型调节剂。
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.
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影响因子：
16.2
作者：
Pietrzykowski AZ;Friesen RM;Martin GE;Puig SI;Nowak CL;Wynne PM;Siegelmann HT;Treistman SN
通讯作者：
Treistman SN
影响因子：
16.2
作者：
Cobos, Inma;Borello, Ugo;Rubenstein, John L. R.
通讯作者：
Rubenstein, John L. R.
DOI：
10.1073/pnas.0609466103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Politz, Joan C. Ritland;Zhang, Fan;Pederson, Thoru
通讯作者：
Pederson, Thoru
影响因子：
4.8
作者：
Giampietro, C;Luzzati, F;Perroteau, I
通讯作者：
Perroteau, I
影响因子：
50.3
作者：
Baldassarre, G;Belletti, B;Colombatti, A
通讯作者：
Colombatti, A