Chen Mengfei, Tian Shenghe, Yang Xiaoling, Lane Andrew P, Reed Randall R, Liu Hongjun
Department of Microbiology and Molecular Genetics and.
Department of Microbiology and Molecular Genetics and Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
J Neurosci. 2014 Jun 11;34(24):8268-76. doi: 10.1523/JNEUROSCI.0240-14.2014.
Persistent neurogenesis in the olfactory epithelium provides a unique model to study neural stem cell self-renewal and fate determination. In the olfactory neuroepithelium, globose basal cells (GBCs) are considered to be the direct progenitors of olfactory neurons. However, the study of neurogenesis from GBCs has been impeded by the paucity of GBC-specific markers. Here we report that Lgr5, a recently discovered adult stem cell marker, is exclusively expressed in GBCs in neonatal and adult mice. Lgr5(+) cells display characteristics of cycling stem cells, including Ki67 expression and EdU incorporation. Lineage tracing analysis demonstrates that Lgr5(+) GBCs regenerate multiple cell types under normal turnover condition or after olfactory lesion. Furthermore, upregulation or downregulation of Wnt signaling in vivo indicates a key role of Wnt signaling not only in maintaining Lgr5(+) cell proliferation and promoting neuroregeneration, but also in delaying sensory neuron maturation. Together, our observations provided new insights into the dynamics of neurogenesis in the olfactory epithelium.
嗅上皮中持续存在的神经发生为研究神经干细胞自我更新和命运决定提供了一个独特的模型。在嗅神经上皮中，球状基底细胞（GBCs）被认为是嗅觉神经元的直接祖细胞。然而，由于缺乏GBC特异性标记物，对GBCs神经发生的研究受到了阻碍。在此，我们报告Lgr5，一种最近发现的成体干细胞标记物，在新生和成年小鼠的GBCs中特异性表达。Lgr5(+)细胞表现出循环干细胞的特征，包括Ki67表达和EdU掺入。谱系追踪分析表明，Lgr5(+) GBCs在正常更新条件下或嗅觉损伤后可再生多种细胞类型。此外，体内Wnt信号的上调或下调表明Wnt信号不仅在维持Lgr5(+)细胞增殖和促进神经再生中起关键作用，而且在延迟感觉神经元成熟中也起关键作用。总之，我们的观察结果为嗅上皮神经发生的动力学提供了新的见解。
