Fibroblast growth factor 10 represses premature cell differentiation during establishment of the intestinal progenitor niche.
Fibroblast growth factor 10 represses premature cell differentiation during establishment of the intestinal progenitor niche.
复制标题
成纤维细胞生长因子10在建立肠道祖细胞生态位期间抑制过早细胞分化。
DOI：
10.1016/j.ydbio.2010.09.010
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发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Jensen J
中科院分区：
文献类型：
--
作者：
Nyeng P;Bjerke MA;Norgaard GA;Qu X;Kobberup S;Jensen J
细胞更新和细胞分化之间平衡的时空调节对于胚胎发育和成人体内平衡至关重要。从间充质传递到上皮的成纤维细胞生长因子信号对于大多数内胚层衍生器官的器官发生过程中祖细胞的维持是必要的，但该信号是否完全是促有丝分裂的仍然不清楚。此外，下游机制很大程度上未知。为了阐明这些问题，我们对胚胎小鼠十二指肠中成纤维细胞生长因子 10 (Fgf10) 功能获得和功能丧失进行了补充分析，其中祖细胞生态位明确定义，分化以空间组织方式进行。与祖细胞维持中的作用一致，FGF10 在早期发育过程中在十二指肠间充质中表达，而同源受体 FGFR2b 在上皮祖细胞生态位中表达。 Fgf10在上皮中的功能获得导致祖细胞生态位的空间扩张和细胞分化的抑制，而功能丧失则导致细胞过早分化和随后的上皮发育不全。我们得出的结论是，FGF10 介导的间充质到上皮信号传导主要通过抑制细胞分化而不是通过促有丝分裂信号传导来维持胚胎十二指肠中的祖细胞生态位。此外，我们证明 FGF10 信号传导靶点包括 ETS 家族转录因子，这些转录因子先前已被证明可以调节上皮成熟和肿瘤进展。
Spatio-temporal regulation of the balance between cell renewal and cell differentiation is of vital importance for embryonic development and adult homeostasis. Fibroblast growth factor signaling relayed from the mesenchyme to the epithelium is necessary for progenitor maintenance during organogenesis of most endoderm-derived organs, but it is still ambiguous whether the signal is exclusively mitogenic. Furthermore, the downstream mechanisms are largely unknown. In order to elucidate these questions we performed a complementary analysis of fibroblast growth factor 10 (Fgf10) gain-of-function and loss-of-function in the embryonic mouse duodenum, where the progenitor niche is clearly defined and differentiation proceeds in a spatially organized manner. In agreement with a role in progenitor maintenance, FGF10 is expressed in the duodenal mesenchyme during early development while the cognate receptor FGFR2b is expressed in the epithelial progenitor niche. Fgf10 gain-of-function in the epithelium leads to spatial expansion of the progenitor niche and repression of cell differentiation, while loss-of-function results in premature cell differentiation and subsequent epithelial hypoplasia. We conclude that FGF10 mediated mesenchymal-to-epithelial signaling maintains the progenitor niche in the embryonic duodenum primarily by repressing cell differentiation, rather than through mitogenic signaling. Furthermore, we demonstrate that FGF10-signaling targets include ETS-family transcription factors, which have previously been shown to regulate epithelial maturation and tumor progression.
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影响因子：
2.7
作者：
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