Neckel Peter Helmut, Mohr Roland, Zhang Ying, Hirt Bernhard, Just Lothar
Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany.
Stem Cells Int. 2016;2016:9695827. doi: 10.1155/2016/9695827. Epub 2015 Nov 30.
Postnatal neural progenitor cells of the enteric nervous system are a potential source for future cell replacement therapies of developmental dysplasia like Hirschsprung's disease. However, little is known about the molecular mechanisms driving the homeostasis and differentiation of this cell pool. In this work, we conducted Affymetrix GeneChip experiments to identify differences in gene regulation between proliferation and early differentiation of enteric neural progenitors from neonatal mice. We detected a total of 1333 regulated genes that were linked to different groups of cellular mechanisms involved in cell cycle, apoptosis, neural proliferation, and differentiation. As expected, we found an augmented inhibition in the gene expression of cell cycle progression as well as an enhanced mRNA expression of neuronal and glial differentiation markers. We further found a marked inactivation of the canonical Wnt pathway after the induction of cellular differentiation. Taken together, these data demonstrate the various molecular mechanisms taking place during the proliferation and early differentiation of enteric neural progenitor cells.
肠道神经系统的产后神经祖细胞是未来用于治疗诸如先天性巨结肠等发育异常疾病的细胞替代疗法的潜在细胞来源。然而,对于驱动这一细胞库的稳态和分化的分子机制,我们知之甚少。在这项研究中,我们进行了Affymetrix基因芯片实验,以鉴定新生小鼠肠道神经祖细胞增殖和早期分化之间的基因调控差异。我们总共检测到1333个受调控基因,这些基因与参与细胞周期、细胞凋亡、神经增殖和分化的不同细胞机制组相关。正如预期的那样,我们发现细胞周期进程的基因表达受到增强的抑制,同时神经元和胶质细胞分化标志物的mRNA表达增强。我们还发现,在细胞分化诱导后,经典Wnt信号通路明显失活。综上所述,这些数据证明了肠道神经祖细胞增殖和早期分化过程中发生的各种分子机制。