Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling
Differentiation of human embryonic stem cells to neural lineages in adherent culture by blocking bone morphogenetic protein signaling
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DOI：
10.1634/stemcells.2005-0110
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发表时间：
2005-10-01
期刊：
影响因子：
5.2
通讯作者：
Cui, W
中科院分区：
文献类型：
--
作者：
Gerrard, L;Rodgers, L;Cui, W
人胚胎干细胞（human embryonic stem cells，hESC）具有广泛的自我更新能力，能够分化为机体的任何细胞类型。它们不仅对人类早期发育的研究有价值，而且对再生医学也有价值。然而，如何引导hESC沿着特定的谱系途径分化为特定的细胞类型仍然是一个挑战。虽然hESC已被证明在体外分化成神经祖细胞，控制其分化的因素知之甚少。在这项研究中，我们报告了一种体外贴壁培养系统的发展，以有效地产生神经祖细胞，其中既不需要多细胞聚集体，也不需要基质细胞。我们发现，通过其拮抗剂头蛋白抑制骨形态发生蛋白信号传导足以阻断胚外细胞的命运，短暂维持Oct4基因表达，并导致神经祖细胞的稳健产生。我们的研究结果将为研究神经分化的分子机制提供一个平台。
Human embryonic stem cells (hESCs) have extensive selfrenewal capacity and are competent to differentiate into any cell type of the body. They are valuable not only for the study of early human development but also for regenerative medicine. However, how to direct differentiation of hESCs along a particular lineage pathway to a specific cell type remains a challenge. Although hESCs have been shown to differentiate in vitro into neural progenitors, the factors controlling their differentiation are poorly understood. In this study, we report the development of an in vitro adherent culture system to efficiently generate neural progenitors in which neither multicellular aggregates nor stromal cells are required. We show that inhibition of bone morphogenetic protein signaling by its antagonist noggin is sufficient to block extraembryonic cell fate, transiently sustain Oct4 gene expression, and result in robust production of neural progenitors. Our findings will provide a platform for studying the molecular mechanism controlling neural differentiation.