Department of Cell and Systems Biology, University of Toronto, 25 Harbord Sreet, Toronto, Ontario M5S 3G5, Canada.
Development. 2013 Nov;140(22):4480-9. doi: 10.1242/dev.096511. Epub 2013 Oct 23.
Imprinted genes play important roles in placenta development and function. Parthenogenetic embryos, deficient in paternally expressed imprinted genes, lack extra-embryonic tissues of the trophoblast lineage. Parthenogenetic trophoblast stem cells (TSCs) are extremely difficult to derive, suggesting that an imprinted gene(s) is necessary for TSC establishment or maintenance. In a candidate study, we were able to narrow the list to one known paternally expressed gene, Sfmbt2. We show that mouse embryos inheriting a paternal Sfmbt2 gene trap null allele have severely reduced placentae and die before E12.5 due to reduction of all trophoblast cell types. We infected early embryos with lentivirus vectors expressing anti-Sfmbt2 shRNAs and found that TSC derivation was significantly reduced. Together, these observations support the hypothesis that loss of SFMBT2 results in defects in maintenance of trophoblast cell types necessary for development of the extra-embryonic tissues, the placenta in particular.
印迹基因在胎盘发育和功能中发挥重要作用。单亲生殖胚胎缺乏父源表达的印迹基因，缺乏滋养层谱系的胚胎外组织。单亲生殖滋养层干细胞（TSC）极难获得，这表明印迹基因（s）对于 TSC 的建立或维持是必要的。在一项候选研究中，我们能够将候选基因缩小到一个已知的父源表达基因 Sfmbt2。我们发现，继承父源 Sfmbt2 基因陷阱无效等位基因的小鼠胚胎由于所有滋养层细胞类型的减少，胎盘严重减少，并在 E12.5 之前死亡。我们用表达抗 Sfmbt2 shRNA 的慢病毒载体感染早期胚胎，发现 TSC 的衍生明显减少。这些观察结果共同支持了这样一种假设，即 SFMBT2 的缺失导致维持滋养层细胞类型的缺陷，而这些细胞类型对于胚胎外组织（特别是胎盘）的发育是必要的。
