Parent stem cells can serve as niches for their daughter cells.
Parent stem cells can serve as niches for their daughter cells.
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亲代干细胞可作为其子代细胞的微环境。
DOI：
10.1038/nature14553
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发表时间：
2015-07-30
期刊：
影响因子：
64.8
通讯作者：
Rajagopal J
中科院分区：
文献类型：
--
作者：
Pardo-Saganta A;Tata PR;Law BM;Saez B;Chow RD;Prabhu M;Gridley T;Rajagopal J
干细胞整合了多种来源的输入。干细胞壁龛提供促进干细胞维持的信号，而分化的子细胞则提供反馈信号来调节干细胞的复制和分化。最近，干细胞被证明可以通过一种自分泌机制来调节自身。“干细胞生态位”的存在是由Schofield于1978年首次提出的，用于定义维持造血干细胞所需的局部环境。从那时起，越来越多的工作集中在定义干细胞龛，，，，，。然而，关于祖细胞和分化细胞的数量和比例是如何维持的，我们知之甚少。在气道上皮中，基底细胞具有干细胞/祖细胞的功能，可以自我更新并产生分化的分泌细胞和纤毛细胞。分泌细胞也作为转运扩增细胞，最终分化为有丝分裂后的纤毛细胞。在这里，我们描述了一种细胞调节模式，其中成年哺乳动物干细胞/祖细胞将向前信号传递给它们自己的后代。令人惊讶的是，这种正向信号被证明是子细胞维持所必需的。通过结合细胞消融、谱系追踪和信号通路调节，我们发现气道基底干/祖细胞持续向其子分泌细胞提供Notch配体。如果没有这些前向信号，分泌祖细胞池就无法维持，分泌细胞就会执行终端分化程序并转化为纤毛细胞。因此，亲本干细胞/祖细胞可以作为功能性子细胞龛。
Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance,, while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation,,,. Recently, stem cells have been shown to regulate themselves using an autocrine mechanism. The existence of a ‘stem cell niche’ was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells. Since then, an increasing body of work has focused on defining stem cell niches,,,,,. Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells,. Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells,. Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche.