Program in Neurodevelopment and Regeneration, Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12770-5. doi: 10.1073/pnas.1202944109. Epub 2012 Jul 3.
Human induced pluripotent stem cells (hiPSCs) are emerging as a tool for understanding human brain development at cellular, molecular, and genomic levels. Here we show that hiPSCs grown in suspension in the presence of rostral neuralizing factors can generate 3D structures containing polarized radial glia, intermediate progenitors, and a spectrum of layer-specific cortical neurons reminiscent of their organization in vivo. The hiPSC-derived multilayered structures express a gene expression profile typical of the embryonic telencephalon but not that of other CNS regions. Their transcriptome is highly enriched in transcription factors controlling the specification, growth, and patterning of the dorsal telencephalon and displays highest correlation with that of the early human cerebral cortical wall at 8-10 wk after conception. Thus, hiPSC are capable of enacting a transcriptional program specifying human telencephalic (pallial) development. This model will allow the study of human brain development as well as disorders of the human cerebral cortex.
人类诱导多能干细胞（hiPSCs）正在成为一种在细胞、分子和基因组水平上理解人类大脑发育的工具。在这里，我们展示了在存在头侧神经化因子的悬浮培养条件下，hiPSCs 可以产生包含极化放射状胶质细胞、中间祖细胞和一系列具有皮质神经元特征的层特异性神经元的 3D 结构，这些神经元类似于其在体内的组织。由 hiPSC 衍生的多层结构表达的基因表达谱典型的胚胎端脑，但不是其他中枢神经系统区域的。它们的转录组高度富集了控制背侧端脑的特化、生长和模式形成的转录因子，并且与人类大脑皮质壁的转录组具有最高的相关性，这是在受孕后 8-10 周。因此，hiPSC 能够实施指定人类端脑（皮层）发育的转录程序。该模型将允许研究人类大脑发育以及人类大脑皮层疾病。
