Sun Y, Nadal-Vicens M, Misono S, Lin M Z, Zubiaga A, Hua X, Fan G, Greenberg M E
Division of Neuroscience, Children's Hospital and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell. 2001 Feb 9;104(3):365-76. doi: 10.1016/s0092-8674(01)00224-0.
The mechanisms by which neural stem cells give rise to neurons, astrocytes, or oligodendrocytes are beginning to be elucidated. However, it is not known how the specification of one cell lineage results in the suppression of alternative fates. We find that in addition to inducing neurogenesis, the bHLH transcription factor neurogenin (Ngn1) inhibits the differentiation of neural stem cells into astrocytes. While Ngn1 promotes neurogenesis by functioning as a transcriptional activator, Ngn1 inhibits astrocyte differentiation by sequestering the CBP-Smad1 transcription complex away from astrocyte differentiation genes, and by inhibiting the activation of STAT transcription factors that are necessary for gliogenesis. Thus, two distinct mechanisms are involved in the activation and suppression of gene expression during cell-fate specification by neurogenin.
神经干细胞分化产生神经元、星形胶质细胞或少突胶质细胞的机制正逐渐被阐明。然而，尚不清楚一种细胞谱系的特化是如何导致其他分化命运受到抑制的。我们发现，bHLH转录因子神经生成素（Ngn1）除了诱导神经发生外，还抑制神经干细胞向星形胶质细胞的分化。Ngn1作为转录激活因子促进神经发生，同时通过将CBP-Smad1转录复合物从星形胶质细胞分化基因上隔离，并抑制神经胶质生成所需的STAT转录因子的激活，从而抑制星形胶质细胞的分化。因此，神经生成素在细胞命运特化过程中，涉及两种不同的机制来激活和抑制基因表达。
