Mikedis Maria M, Downs Karen M
Department of Cell and Regenerative Biology, University of Wisconsin-Madison School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA.
Gene Expr Patterns. 2013 Oct;13(7):225-39. doi: 10.1016/j.gep.2013.04.003. Epub 2013 Apr 29.
Interferon-induced transmembrane protein 3 (IFITM3; FRAGILIS; MIL-1) is part of a larger family of important small interferon-induced transmembrane genes and proteins involved in early development, cell adhesion, and cell proliferation, and which also play a major role in response to bacterial and viral infections and, more recently, in pronounced malignancies. IFITM3, together with tissue-nonspecific alkaline phosphatase (TNAP), PRDM1, and STELLA, has been claimed to be a hallmark of segregated primordial germ cells (PGCs) (Saitou et al., 2002). However, whether IFITM3, like STELLA, is part of a broader stem/progenitor pool that builds the posterior region of the mouse conceptus (Mikedis and Downs, 2012) is obscure. To discover the whereabouts of IFITM3 during mouse gastrulation (~E6.5-9.0), systematic immunohistochemical analysis was carried out at closely spaced 2-4-h intervals. Results revealed diverse, yet consistent, profiles of IFITM3 localization throughout the gastrula. Within the putative PGC trajectory and surrounding posterior tissues, IFITM3 localized as a large cytoplasmic spot with or without staining in the plasma membrane. IFITM3, like STELLA, was also found in the ventral ectodermal ridge (VER), a posterior progenitor pool that builds the tailbud. The large cytoplasmic spot with plasma membrane staining was exclusive to the posterior region; the visceral yolk sac, non-posterior tissues, and epithelial tissues exhibited spots of IFITM3 without cell surface staining. Colocalization of the intracellular IFITM3 spot with the endoplasmic reticulum, Golgi apparatus, or endolysosomes was not observed. That relatively high levels of IFITM3 were found throughout the posterior primitive streak and its derivatives is consistent with evidence that IFITM3, like STELLA, is part of a larger stem/progenitor cell pool at the posterior end of the primitive streak that forms the base of the allantois and builds the fetal-umbilical connection, thus further obfuscating practical phenotypic distinctions between so-called PGCs and surrounding soma.
干扰素诱导跨膜蛋白3（IFITM3；FRAGILIS；MIL-1）是一个更大的重要小干扰素诱导跨膜基因和蛋白家族的一部分，这些基因和蛋白参与早期发育、细胞黏附以及细胞增殖，并且在应对细菌和病毒感染中发挥主要作用，最近还发现其在显著的恶性肿瘤中也起作用。IFITM3与组织非特异性碱性磷酸酶（TNAP）、PRDM1以及STELLA一起，被认为是分离的原始生殖细胞（PGC）的一个标志（Saitou等人，2002年）。然而，IFITM3是否像STELLA一样，是构建小鼠胚胎后部区域的更广泛的干细胞/祖细胞池的一部分（Mikedis和Downs，2012年）尚不清楚。为了发现IFITM3在小鼠原肠胚形成期间（约E6.5 - 9.0）的位置，以紧密间隔的2 - 4小时间隔进行了系统的免疫组织化学分析。结果揭示了IFITM3在整个原肠胚中的定位情况多样但一致。在假定的PGC轨迹及其周围的后部组织中，IFITM3定位为一个大的细胞质斑点，质膜上有或没有染色。与STELLA一样，IFITM3也在腹侧外胚层嵴（VER）中被发现，VER是构建尾芽的后部祖细胞池。质膜染色的大细胞质斑点是后部区域所特有的；内脏卵黄囊、非后部组织和上皮组织中IFITM3的斑点没有细胞表面染色。未观察到细胞内IFITM3斑点与内质网、高尔基体或内溶酶体的共定位。在整个后部原始条纹及其衍生物中发现相对高水平的IFITM3，这与IFITM3像STELLA一样是原始条纹后端更大的干细胞/祖细胞池的一部分的证据一致，该池形成尿囊的基部并构建胎儿 - 脐带连接，从而进一步模糊了所谓的PGC与周围体细胞之间实际的表型差异。
