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Niche Cells and Signals that Regulate Lung Alveolar Stem Cells In Vivo.
Cold Spring Harbor Perspectives in Biology ( IF 6.9 ) Pub Date : 2020-12-01 , DOI: 10.1101/cshperspect.a035717
Nicholas H Juul 1, 2 , Courtney A Stockman 2 , Tushar J Desai 1, 2
Affiliation  

The distal lung is a honeycomb-like collection of delicate gas exchange sacs called alveoli lined by two interspersed epithelial cell types: the cuboidal, surfactant-producing alveolar type II (AT2) and the flat, gas-exchanging alveolar type I (AT1) cell. During aging, a subset of AT2 cells expressing the canonical Wnt target gene, Axin2, function as stem cells, renewing themselves while generating new AT1 and AT2 cells. Wnt activity endows AT2 cells with proliferative competency, enabling them to respond to activating cues, and simultaneously blocks AT2 to AT1 cell transdifferentiation. Acute alveolar injury rapidly expands the AT2 stem cell pool by transiently inducing Wnt signaling activity in “bulk” AT2 cells, facilitating rapid epithelial repair. AT2 cell “stemness” is thus tightly regulated by access to Wnts, supplied by a specialized single-cell fibroblast niche during maintenance and by AT2 cells themselves during injury repair. Two non-AT2 “reserve” cell populations residing in the distal airways also contribute to alveolar repair, but only after widespread epithelial injury, when they rapidly proliferate, migrate, and differentiate into airway and alveolar lineages. Here, we review alveolar renewal and repair with a focus on the niches, rather than the stem cells, highlighting what is known about the cellular and molecular mechanisms by which they control stem cell activity in vivo.

中文翻译:


体内调节肺泡干细胞的利基细胞和信号。



远端肺是一个蜂窝状的精致气体交换囊集合,称为肺泡,内衬两种散布的上皮细胞类型:产生表面活性剂的立方形 II 型肺泡 (AT2) 和扁平的气体交换 I 型肺泡 (AT1) 细胞。在衰老过程中,表达经典Wnt靶基因Axin2的 AT2 细胞子集充当干细胞,在产生新的 AT1 和 AT2 细胞的同时进行自我更新。 Wnt活性赋予 AT2 细胞增殖能力,使其能够对激活信号做出反应,并同时阻止 AT2 细胞向 AT1 细胞转分化。急性肺泡损伤通过在“大量”AT2 细胞中瞬时诱导Wnt信号活性来快速扩大 AT2 干细胞库,从而促进快速上皮修复。因此,AT2 细胞的“干性”受到Wnt的严格调控,Wnt 是在维持过程中由专门的单细胞成纤维细胞生态位提供的,在损伤修复过程中是由 AT2 细胞本身提供的。存在于远端气道中的两个非 AT2“储备”细胞群也有助于肺泡修复,但只有在广泛的上皮损伤之后,它们才能快速增殖、迁移并分化为气道和肺泡谱系。在这里,我们回顾了肺泡的更新和修复,重点关注微环境,而不是干细胞,强调了它们控制体内干细胞活性的细胞和分子机制的已知信息。
更新日期:2020-12-02
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