Age-Dependent Activation and Neuronal Differentiation of Lgr5+ Basal Cells in Injured Olfactory Epithelium via Notch Signaling Pathway.
Age-Dependent Activation and Neuronal Differentiation of Lgr5+ Basal Cells in Injured Olfactory Epithelium via Notch Signaling Pathway.
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损伤嗅上皮中 Lgr5 基底细胞通过 Notch 信号通路的年龄依赖性激活和神经元分化
DOI：
10.3389/fnagi.2020.602688
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发表时间：
2020
影响因子：
4.8
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Li X;Tong M;Wang L;Qin Y;Yu H;Yu Y
衰老是影响嗅觉功能的一个重要因素，导致成熟的嗅觉神经元退化，导致嗅觉丧失的发生。哺乳动物的嗅上皮在化学物质的作用下可以再生。然而，这种能力不是无限的。基底细胞的失活和感觉神经元的再生障碍是阻碍OE再生的主要原因。在这里，我们发现了显着衰减，在成熟的感觉神经元的产生和明显的转录改变，从老年小鼠相比，年轻的OE。在老年小鼠中，富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5）阳性细胞在损伤的OE中的募集减弱，并且更多的Lgr5+细胞在老年OE损伤后保持静止。血统追溯后代从Lgr5+细胞显着较少的OE与老化。此外，Notch激活增强了老年OE中的神经元再生，使得老年OE的再生能力与损伤后的年轻动物相当。来自年轻和老年小鼠OE的三维（3D）培养的类器官的生长和形态各不相同，并且由调节Notch信号通路的小分子调节。因此，我们的结论是，激活Lgr5+细胞在受伤的OE是年龄依赖性的和Notch激活可以增强的能力，从Lgr5+细胞在老年OE损伤后神经元的产生。
Aging is an important factor affecting function of smell, leading to the degeneration of mature olfactory sensory neurons and inducing the occurrence of smell loss. The mammalian olfactory epithelium (OE) can regenerate when subjected to chemical assaults. However, this capacity is not limitless. Inactivation of globose basal cells and failure to generate sensory neurons are the main obstacles to prevent the OE regeneration. Here, we found the significant attenuation in mature sensory neuronal generation and apparent transcriptional alternation in the OE from aged mice compared with young ones. The recruitment of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5)-positive cells in injured OE was weakened in aged mice, and more Lgr5+ cells remained quiescence in aged OE postinjury. Lineage-traced progenies from Lgr5+ cells were significantly fewer in the OE with aging. Moreover, Notch activation enhanced the neuronal regeneration in aged OE, making the regenerative capacity of aged OE comparable with that of young animals after injury. The growth and morphology of three-dimensional (3D)-cultured organoids from the OE of young and aged mice varied and was modulated by small molecules regulating the Notch signaling pathway. Thus, we concluded that activation of Lgr5+ cells in injured OE was age dependent and Notch activation could enhance the capacity of neuronal generation from Lgr5+ cells in aged OE after injury.
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DOI：
10.1002/dvdy.24416
发表时间：
2016-07
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Richmond CA;Shah MS;Carlone DL;Breault DT
通讯作者：
Breault DT
影响因子：
16.6
作者：
Jung KB;Lee H;Son YS;Lee MO;Kim YD;Oh SJ;Kwon O;Cho S;Cho HS;Kim DS;Oh JH;Zilbauer M;Min JK;Jung CR;Kim J;Son MY
通讯作者：
Son MY
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
5.3
作者：
Herrick, Daniel B.;Guo, Zhen;Schwob, James E.
通讯作者：
Schwob, James E.
影响因子：
5.3
作者：
Child, Kevin M.;Herrick, Daniel B.;Jang, Woochan
通讯作者：
Jang, Woochan