Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells
Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells
复制标题
DOI：
10.1073/pnas.1037282100
复制
发表时间：
2003-05-13
影响因子：
11.1
通讯作者：
Sasai, Y
中科院分区：
文献类型：
--
作者：
Mizuseki, K;Sakamoto, T;Sasai, Y
为了解胚胎干细胞（ES）衍生的神经前体细胞的分化能力范围，我们研究了小鼠和灵长类ES细胞在体外分化为神经轴背侧（神经嵴）和最腹侧（底板）细胞的情况。基质细胞衍生的诱导活性（SDIA；在PA6基质细胞上积累）诱导共培养的ES细胞分化为包含腹侧和背侧细胞的头侧中枢神经系统组织。尽管SDIA处理的ES细胞早期暴露于骨形态发生蛋白（BMP）4会抑制神经分化并促进表皮发生，但共培养第4天后晚期暴露于BMP4会导致神经嵴细胞和最背侧中枢神经系统细胞分化，其中高浓度和低浓度的BMP4分别优先诱导自主神经系统和感觉谱系。相比之下，音猬因子（Shh）抑制神经嵴谱系的分化并促进腹侧中枢神经系统组织如运动神经元的分化。值得注意的是，高浓度的Shh可有效促进具有轴突导向活性的HNF3β（+）底板细胞的分化。因此，经SDIA处理的ES细胞产生原始前体细胞，这些细胞具有响应模式形成信号分化为神经外胚层衍生物的“完整”背腹侧范围的能力。
To understand the range of competence of embryonic stem (ES) cell-derived neural precursors, we have examined in vitro differentiation of mouse and primate ES cells into the dorsal- (neural crest) and ventralmost (floor plate) cells of the neural axis. Stromal cell-derived inducing activity (SDIA; accumulated on PA6 stromal cells) induces cocultured ES cells to differentiate into rostral CNS tissues containing both ventral and dorsal cells. Although early exposure of SDIA-treated ES cells to bone morphogenetic protein (BMP)4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the fourth day of coculture causes differentiation of neural crest cells and dorsalmost CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons. Notably, high concentrations of Shh efficiently promote differentiation of HNF3beta(+) floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naive precursors that have the competence of differentiating into the "full" dorsal-ventral range of neuroectodermal derivatives in response to patterning signals.