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发出Lrig1的静止干细胞通过Notch信号来维持声粘膜平衡
Vlasta Lungova1, Jessica M Fernandez1, Yujia Cai2
1Department of Otolaryngology Head and Neck Surgery, University of Wisconsin Madison, Madison, WI 53705.
概括
研究人员确定了Lrig1 (富含白的重复和免疫球蛋白类域1) 作为喉和声中静止干细胞的标记物. 这些Lrig1+细胞对于组织恒温和再生至关重要,它们的静止受Notch1信号调节.
科学领域:
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
- 喉的解剖学 喉的解剖学
背景情况:
- 在喉和声 (VF) 粘膜中识别原生细胞对于开发有效的VF疾病干细胞治疗非常重要.
- 了解VF恒温和再生的细胞机制对于治疗语音障碍至关重要.
研究的目的:
- 使用Lrig1基因识别和描述喉和VF粘膜中的组织居民干细胞.
- 为了研究Lrig1+细胞在VF再生和恒温的作用.
- 探索调节机制,特别是Notch1信号传递,参与维持这些干细胞的静止状态.
主要方法:
- 利用Lrig1基因标记和跟踪喉和VF粘膜中的组织居民干细胞.
- 评估Lrig1+细胞的干细胞特征 (静止,增殖,分化潜力).
- 诱导甲烯损伤模型VF损伤,并观察到Lrig1+后代的再生能力.
- 进行了Lrig1+细胞的转录分析.
- 进行了Notch1的条件删除,以研究其在调节Lrig1+细胞静止中的作用.
- 在人类喉和VF组织中检查了类似的LRIG1表达细胞.
主要成果:
- Lrig1+细胞表现出静止干细胞特征,包括缓慢循环,长期持久性和分化潜力.
- 在受伤后一周内,Lrig1+后代有效地恢复了受损的VF表皮.
- 转录分析显示,Lrig1+细胞抑制增殖基因,同时激活RNA代谢,表观遗传调节和蛋白质无处不在的程序.
- 发现Lrig1+细胞位于表皮和下腺的特定中,具有转录灵活性和空间屏蔽的特征.
- 条件删除Notch1导致上皮质增生,分泌细胞数量增加和粘液过度产生.
- 在人类喉和VF组织中鉴定了同源的LRIG1表达细胞.
结论:
- Lrig1标志着喉和声中保存,静止的干细胞群,这对于长期组织平衡和修复至关重要.
- 诺奇1信号传递在维持Lrig1+干细胞的静止状态方面发挥着至关重要的作用,防止异常增殖和粘液过度产生.
- 这些发现对于开发用于声疾病的基于干细胞的疗法具有重要的翻译意义.
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