Okabe S, Forsberg-Nilsson K, Spiro A C, Segal M, McKay R D
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Mech Dev. 1996 Sep;59(1):89-102. doi: 10.1016/0925-4773(96)00572-2.
To understand the mechanism of the sequential restriction of multipotency of stem cells during development, we have established culture conditions that allow the differentiation of neuroepithelial precursor cells from embryonic stem (ES) cells. A highly enriched population of neuroepithelial precursor cells derived from ES cells proliferates in the presence of basic fibroblast growth factor (bFGF). These cells differentiate into both neurons and glia following withdrawal of bFGF. By further differentiating the cells in serum-containing medium, the neurons express a wide variety of neuron-specific genes and generate both excitatory and inhibitory synaptic connections. The expression pattern of position-specific neural markers suggests the presence of a variety of central nervous system (CNS) neuronal cell types. These findings indicate that neuronal precursor cells can be isolated from ES cells and that these cells can efficiently differentiate into functional post-mitotic neurons of diverse CNS structures.
为了理解干细胞多能性在发育过程中受到顺序性限制的机制，我们建立了能够使胚胎干细胞（ES细胞）分化为神经上皮前体细胞的培养条件。源自ES细胞的高度富集的神经上皮前体细胞群体在碱性成纤维细胞生长因子（bFGF）存在的情况下增殖。去除bFGF后，这些细胞会分化为神经元和神经胶质细胞。通过在含血清培养基中进一步分化这些细胞，神经元表达多种神经元特异性基因，并形成兴奋性和抑制性突触连接。位置特异性神经标志物的表达模式表明存在多种中枢神经系统（CNS）神经元细胞类型。这些发现表明，可以从ES细胞中分离出神经元前体细胞，并且这些细胞能够有效地分化为具有不同CNS结构的功能性有丝分裂后神经元。
