Leung Cheuk T, Coulombe Pierre A, Reed Randall R
Center for Sensory Biology and the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, PCTB 801, Baltimore, Maryland 21205, USA.
Nat Neurosci. 2007 Jun;10(6):720-6. doi: 10.1038/nn1882. Epub 2007 Apr 29.
The olfactory neuroepithelium undergoes continual neurogenesis and, after extensive lesions, fully regenerates to maintain sensory function. The stem cell population underlying this regenerative capacity remains elusive. Here we show that mouse horizontal basal cells (HBCs) function as adult olfactory neuroepithelium neural stem cells and examine their distinct dynamics in olfactory neuroepithelium maintenance and regeneration. Fate-mapping analysis after olfactory neuroepithelium lesioning shows that HBCs are competent to regenerate both neuronal and non-neuronal olfactory neuroepithelium lineages. HBCs serve as a reservoir of long-lived progenitors that remain largely quiescent during normal neuronal turnover or even after acute, selective loss of mature neurons. Under these conditions, previously identified progenitors are largely responsible for tissue maintenance. Yet after extensive injuries that deplete resident neuronal precursors, HBCs transiently proliferate and their progeny fully reconstitute the neuroepithelium. Our data support a new model of adult neurogenesis in which distinct cell populations mediate normal neuronal turnover and neuronal replacement upon traumatic injury.
嗅觉神经上皮会持续进行神经发生，在受到广泛损伤后能完全再生以维持感觉功能。这种再生能力背后的干细胞群体仍然难以捉摸。在此，我们表明小鼠水平基底细胞（HBCs）作为成体嗅觉神经上皮神经干细胞发挥作用，并研究了它们在嗅觉神经上皮维持和再生过程中的独特动态变化。嗅觉神经上皮损伤后的命运图谱分析表明，HBCs有能力再生神经元和非神经元嗅觉神经上皮谱系。HBCs作为长寿祖细胞的储存库，在正常神经元更新过程中甚至在成熟神经元急性、选择性丧失后，它们大多保持静止。在这些情况下，先前确定的祖细胞在很大程度上负责组织维持。然而，在广泛损伤耗尽驻留神经元前体细胞后，HBCs会短暂增殖，其后代会完全重建神经上皮。我们的数据支持了一种成体神经发生的新模型，即不同的细胞群体介导正常的神经元更新以及创伤性损伤后的神经元替代。
