Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage
Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage
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DOI：
10.1634/stemcells.2006-0707
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发表时间：
2007-06-01
期刊：
影响因子：
5.2
通讯作者：
Zhang, Su-Chun
中科院分区：
文献类型：
--
作者：
Pankratz, Matthew T.;Li, Xue-Jun;Zhang, Su-Chun
了解神经外胚层的形成和随后向功能性神经亚型的分化仍然难以捉摸。我们在这里展示了人类胚胎干细胞（hESCs）在8-10天后分化为原始神经外胚层。在这个阶段，细胞均匀地呈现柱状形态，并表达神经标记物，包括前同源结构域蛋白，但不包括后同源结构域蛋白。在最初的神经外胚层发育过程中，不管形成因子如何，这些细胞的前身份都会发育。在接下来的一周内，这种前表型可以维持或转化为具有特定形态因子的尾侧表型，当细胞成为最终的神经上皮时，其特征是具有明显粘附分子表达的神经管样结构，Sox1表达，以及对其他模式信号的抵抗。因此，原始神经上皮代表了最早的神经细胞，具有分化为区域特异性神经祖细胞的潜力。这一发现提供了对早期人类大脑发育的见解，并为产生具有正确位置和递质谱的神经细胞奠定了基础。
Understanding neuroectoderm formation and subsequent diversification to functional neural subtypes remains elusive. We show here that human embryonic stem cells (hESCs) differentiate to primitive neuroectoderm after 8-10 days. At this stage, cells uniformly exhibit columnar morphology and express neural markers, including anterior but not posterior homeodomain proteins. The anterior identity of these cells develops regardless of morphogens present during initial neuroectoderm specification. This anterior phenotype can be maintained or transformed to a caudal fate with specific morphogens over the next week, when cells become definitive neuroepithelia, marked by neural tube-like structures with distinct adhesion molecule expression, Sox1 expression, and a resistance to additional patterning signals. Thus, primitive neuroepithelia represents the earliest neural cells that possess the potential to differentiate to regionally specific neural progenitors. This finding offers insights into early human brain development and lays a foundation for generating neural cells with correct positional and transmitter profiles.