Lgr5(+) cells are required and dynamically participate in olfactory epithelium regeneration: a revisiting shows Lgr5 expression in multiple cell lineages.
Lgr5(+) cells are required and dynamically participate in olfactory epithelium regeneration: a revisiting shows Lgr5 expression in multiple cell lineages.
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DOI：
10.7150/thno.60636
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发表时间：
2022
期刊：
影响因子：
12.4
通讯作者：
Yu, Yiqun
中科院分区：
文献类型：
--
作者：
Ren, Wenwen;Ma, Zhenjie;Wang, Li;Feng, Xiaoyu;Yu, Hongmeng;Yu, Yiqun
关键词：
嗅觉感觉神经元（OSNs）位于嗅觉上皮（OE）中，能够检测到数千种挥发性的环境气味，从而形成嗅觉。osn来源于基底细胞，具有祖细胞/干细胞的特征。在哺乳动物OE中，持续的神经发生发生在一生中，为研究干细胞的组织更新和命运决定提供了一个独特的模型。方法：免疫组织化学分析和RNAscope原位杂交表明，在完整和损伤的OE中存在富含亮氨酸的含重复g蛋白偶联受体5 （Lgr5）。通过谱系追踪分析Lgr5+细胞在OE稳态和再生中的动态作用。我们还利用dtr驱动的Lgr5+细胞基因缺失和慢病毒介导的Lgr5下调来证明Lgr5+细胞在OE再生中的重要作用。结果：我们发现Lgr5在成人OE中标记水平基底细胞（HBCs），而不是新生儿。我们回顾了Lgr5+细胞在OE稳态和再生中的作用，发现Lgr5+细胞参与了新生儿至1月龄OE稳态以及损伤后OE再生。在OE再生过程中，Lgr5在顶端支持细胞、未成熟神经元和成熟感觉神经元中短暂表达。Lgr5+细胞在再生的OE中变成或生成HBCs。dtr驱动的细胞耗竭表明Lgr5+细胞在成人OE稳态中不是必需的，但在OE损伤恢复中却是必需的。慢病毒感染对Lgr5的下调也证明了Lgr5表达在OE再生中的重要作用。结论：我们的研究阐明了Lgr5+细胞在OE稳态和再生中的作用，可能为基于细胞的治疗嗅觉功能障碍提供了一种候选方法。
Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated from basal cells, which show the characteristics of progenitor/stem cells. In the mammalian OE, persistent neurogenesis occurs during lifetime, providing a unique model to study the tissue turnover and fate determination of stem cells. Methods: Immunohistochemical analysis and RNAscope in situ hybridization indicated the localization of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) in the intact and injured OE. Lineage tracing was conducted to analyze the dynamic role of Lgr5+ cells in the OE homeostasis and regeneration. We also used DTR-driven genetic depletion of Lgr5+ cells and lentivirus-mediated Lgr5 downregulation to demonstrate the essential role of Lgr5+ cells in the OE regeneration. Results: We show that Lgr5 marks horizontal basal cells (HBCs) in the OE of adults but not newborns. We revisit the role of Lgr5+ cells in the OE homeostasis and regeneration, and find that Lgr5+ cells participate in the OE homeostasis from neonatal to one-month-old age, as well as in the OE regeneration post injury. During the OE regeneration, Lgr5 is transiently expressed in apical supporting cells, immature neurons, and mature sensory neurons. The Lgr5+ cells become or generate HBCs in the regenerated OE. DTR-driven cell depletion shows that Lgr5+ cells are not necessary in the adult OE homeostasis, but required in the recovery of OE from injury. Lgr5 down-regulation by lentiviral infection also demonstrates the essential role of Lgr5 expression in the OE regeneration. Conclusion: Our study elucidates the role of Lgr5+ cells in the OE homeostasis and regeneration, potentially providing a candidate to cell-based therapy against olfactory dysfunction.
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影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
DOI：
10.1523/jneurosci.0681-11.2011
发表时间：
2011-06-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Packard A;Schnittke N;Romano RA;Sinha S;Schwob JE
通讯作者：
Schwob JE
影响因子：
8.8
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
2.5
作者：
Manglapus, GL;Youngentob, SL;Schwob, JE
通讯作者：
Schwob, JE
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
影响因子：
4.8
作者：
Li X;Tong M;Wang L;Qin Y;Yu H;Yu Y
通讯作者：
Yu Y