Guzman-Ayala Marcela, Ben-Haim Nadav, Beck Séverine, Constam Daniel B
Developmental Biology Group, Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15656-60. doi: 10.1073/pnas.0405429101. Epub 2004 Oct 25.
Before implantation in the uterus, mammalian embryos set aside trophoblast stem cells that are maintained in the extraembryonic ectoderm (ExE) during gastrulation to generate the fetal portion of the placenta. Their proliferation depends on diffusible signals from neighboring cells in the epiblast, including fibroblast growth factor 4 (Fgf4). Here, we show that Fgf4 expression is induced by the transforming growth factor beta-related protein Nodal. Together with Fgf4, Nodal also acts directly on neighboring ExE to sustain a microenvironment that inhibits precocious differentiation of trophoblast stem cells. Because the ExE itself produces the proteases Furin and PACE4 to activate Nodal, it represents the first example, to our knowledge, of a stem cell compartment that actively maintains its own microenvironment.
在植入子宫之前，哺乳动物胚胎会预留出滋养层干细胞，这些细胞在原肠胚形成过程中维持在外胚层（ExE）中，以生成胎盘的胎儿部分。它们的增殖依赖于来自上胚层相邻细胞的可扩散信号，包括成纤维细胞生长因子4（Fgf4）。在这里，我们表明Fgf4的表达是由转化生长因子β相关蛋白Nodal诱导的。与Fgf4一起，Nodal还直接作用于相邻的ExE，以维持一种抑制滋养层干细胞过早分化的微环境。由于ExE自身会产生蛋白酶弗林蛋白酶（Furin）和PACE4来激活Nodal，据我们所知，它代表了一个主动维持自身微环境的干细胞区室的首个例子。
