Combined KIT and FGFR2b signaling regulates epithelial progenitor expansion during organogenesis.
Combined KIT and FGFR2b signaling regulates epithelial progenitor expansion during organogenesis.
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DOI：
10.1016/j.stemcr.2013.10.013
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发表时间：
2013
影响因子：
5.9
通讯作者：
Hoffman, Matthew P.
中科院分区：
文献类型：
--
作者：
Lombaert, Isabelle M. A.;Abrams, Shaun R.;Li, Li;Eswarakumar, Veraragavan P.;Sethi, Aditya J.;Witt, Robert L.;Hoffman, Matthew P.
器官形成和再生需要上皮祖细胞扩增以工程化、维持和修复分支组织结构。确定控制祖细胞扩增的机制将为治疗性器官（再生）提供信息。在这里，我们发现，结合KIT和成纤维细胞生长因子受体2b（FGFR 2b）信号特异性地增加远端祖细胞扩张在唾液腺器官发生。FGFR 2b信号转导上调上皮KIT途径，使得组合的KIT/FGFR 2b信号转导通过单独的AKT和促分裂原活化蛋白激酶（MAPK）途径放大FGFR 2b依赖性转录。组合的KIT/FGFR 2b信号传导选择性地扩增KIT+K14+ S 0X 10+远端祖细胞的数量，并且KIT信号传导的遗传缺失耗尽远端祖细胞，但也意外地耗尽K5+近端祖细胞。这是因为远端祖细胞产生支持腺体神经支配的神经营养因子，从而维持近端祖细胞。此外，一种罕见的KIT+ FGFR 2b+细胞群体存在于成年腺体中，其中KIT信号传导还调节稳态期间的上皮-神经元通讯。我们的研究结果提供了一个框架，以指导再生的分支上皮器官。KIT和FGFR 2b信号的组合在器官形成期间放大FGFR 2b依赖性转录KIT/FGFR 2b信号在器官形成期间扩展远端KIT+上皮祖细胞远端祖细胞通过神经元龛与近端祖细胞通信KIT+祖细胞在成体稳态期间维持上皮-神经元通信霍夫曼及其同事证明，KIT和成纤维细胞生长因子受体2b（FGFR 2b）信号的组合在器官形成期间扩展远端KIT+ FGFR 2b+上皮祖细胞分支器官中的祖先群体。这对于持续的分支形态发生是重要的，因为KIT+ FGFR 2b+祖细胞产生神经营养因子以与神经元生态位通信，从而指导近端角蛋白5+祖细胞的导管分化。
Organ formation and regeneration require epithelial progenitor expansion to engineer, maintain, and repair the branched tissue architecture. Identifying the mechanisms that control progenitor expansion will inform therapeutic organ (re)generation. Here, we discover that combined KIT and fibroblast growth factor receptor 2b (FGFR2b) signaling specifically increases distal progenitor expansion during salivary gland organogenesis. FGFR2b signaling upregulates the epithelial KIT pathway so that combined KIT/FGFR2b signaling, via separate AKT and mitogen-activated protein kinase (MAPK) pathways, amplifies FGFR2b-dependent transcription. Combined KIT/FGFR2b signaling selectively expands the number of KIT+K14+SOX10+ distal progenitors, and a genetic loss of KIT signaling depletes the distal progenitors but also unexpectedly depletes the K5+ proximal progenitors. This occurs because the distal progenitors produce neurotrophic factors that support gland innervation, which maintains the proximal progenitors. Furthermore, a rare population of KIT+FGFR2b+ cells is present in adult glands, in which KIT signaling also regulates epithelial-neuronal communication during homeostasis. Our findings provide a framework to direct regeneration of branched epithelial organs. Combined KIT and FGFR2b signaling amplifies FGFR2b-dependent transcription KIT/FGFR2b signaling during organogenesis expands distal KIT+ epithelial progenitors Distal progenitors communicate with proximal progenitors via the neuronal niche KIT+ progenitors maintain epithelial-neuronal communication during adult homeostasis Hoffman and colleagues demonstrate that combined KIT and fibroblast growth factor receptor 2b (FGFR2b) signaling expands the distal KIT+FGFR2b+ progenitor population in branching organs. This is important for continued branching morphogenesis because the KIT+FGFR2b+ progenitors produce neurotrophic factors to communicate with the neuronal niche to direct the ductal differentiation of proximal Keratin 5+ progenitors.
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DOI：
10.1152/ajpendo.00172.2007
发表时间：
2007-08-01
影响因子：
5.1
作者：
Li, Jinming;Quirt, Jaclyn;Wang, Rennian
通讯作者：
Wang, Rennian
干细胞移植在辐照腺体中的干细胞移植后拯救唾液腺功能。
影响因子：
3.7
作者：
Lombaert, Isabelle M. A.;Brunsting, Jeanette F.;Wierenga, Pieter K.;Faber, Hette;Stokman, Monique A.;Kok, Tineke;Visser, Willy H.;Kampinga, Harm H.;de Haan, Gerald;Coppes, Robert P.
通讯作者：
Coppes, Robert P.
影响因子：
4.6
作者：
Lin, Yongshun;Liu, Guoqin;Wang, Fen
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Wang, Fen
影响因子：
64.8
作者：
Kiger, AA;White-Cooper, H;Fuller, MT
通讯作者：
Fuller, MT
影响因子：
20.3
作者：
Jahn, Thomas;Sindhu, Simran;Weinberg, Kenneth
通讯作者：
Weinberg, Kenneth