Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells.
Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells.
复制标题
成纤维细胞生长因子10 - 河马信号通路的上皮 - 间充质相互作用维持并招募肺基底干细胞。
DOI：
10.1016/j.devcel.2017.09.003
复制
发表时间：
2017-10-09
影响因子：
11.8
通讯作者：
De Langhe SP
中科院分区：
文献类型：
--
作者：
Volckaert T;Yuan T;Chao CM;Bell H;Sitaula A;Szimmtenings L;El Agha E;Chanda D;Majka S;Bellusci S;Thannickal VJ;Fässler R;De Langhe SP
肺将其基底干/祖细胞（BSC）容纳在软骨气道的受保护环境中。在严重的肺损伤后，BSC被激活并募集到损伤部位。在这里，我们表明，在体内平衡，在软骨气道的BSC维持其干细胞状态下调Hippo通路（导致增加核雅普），这产生了一个本地化的Fgf 10表达的基质生态位;相反，在非软骨气道分化的上皮细胞通过激活Hippo通路和抑制气道平滑肌细胞（ASMC）的Fgf 10表达保持静止。然而，在损伤后，存活的分化上皮细胞扩散以维持屏障功能并将整合素连接的激酶募集至粘附位点，这导致Merlin降解、Hippo途径的下调、核雅普易位以及Wnt 7 b的表达和分泌。上皮来源的Wnt 7 b继而诱导ASMCs中的Fgf 10表达，其扩展BSC生态位以促进再生。Volckaert等人证明了一种新的干细胞调节模式，其中稳态期间的基底干细胞或损伤后分化的气道上皮细胞下调其Hippo信号传导，以产生其自身的局部表达Fgf 10的基质小生境，其通过Fgf 10-Fgfr 2b信号传导维持或扩增干/祖细胞群体。
The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by down-regulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10 expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs). However, upon injury, surviving differentiated epithelial cells spread to maintain barrier function and recruit integrin linked kinase to adhesion sites, which leads to Merlin degradation, down-regulation of the Hippo pathway, nuclear Yap translocation and expression and secretion of Wnt7b. Epithelial-derived Wnt7b, then in turn, induces Fgf10 expression in ASMCs which extends the BSC niche to promote regeneration. Volckaert et al. demonstrate a novel mode of stem cell regulation in which basal stem cells during homeostasis or differentiated airway epithelial cells after injury down-regulate their Hippo signaling to generate their own localized Fgf10-expressing stromal niche, which maintains or amplifies the stem/progenitor cell population via Fgf10-Fgfr2b signaling.
登录
查看更多内容
影响因子：
64.5
作者：
Kumar PA;Hu Y;Yamamoto Y;Hoe NB;Wei TS;Mu D;Sun Y;Joo LS;Dagher R;Zielonka EM;Wang de Y;Lim B;Chow VT;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
影响因子：
64.8
作者：
Peng T;Frank DB;Kadzik RS;Morley MP;Rathi KS;Wang T;Zhou S;Cheng L;Lu MM;Morrisey EE
通讯作者：
Morrisey EE
影响因子：
13.5
作者：
Apte, Udayan;Gkretsi, Vasiliki;Bowen, William C.;Mars, Wendy M.;Luo, Jian-Hua;Donthamsetty, Shashikiran;Orr, Ann;Monga, Satdarshan P. S.;Wu, Chuanyue;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.
对 NF2/Merlin 肿瘤抑制功能的分子见解。
影响因子：
3.5
作者：
Cooper J;Giancotti FG
通讯作者：
Giancotti FG
影响因子：
8
作者：
Ji, H;Houghton, AM;Wong, KK
通讯作者：
Wong, KK