Tompers Dennie M, Foreman Ruth K, Wang Qiaohong, Kumanova Monika, Labosky Patricia A
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104-6058, USA.
Dev Biol. 2005 Sep 1;285(1):126-37. doi: 10.1016/j.ydbio.2005.06.008.
The murine blastocyst contains two nonoverlapping pools of progenitor cells: the embryonic component contributes to the fetus and generates embryonic stem cells in vitro, whereas the extraembryonic pool contributes to the placenta and generates trophoblast stem cells in vitro. The transcriptional repressor Foxd3 is required for maintenance of the epiblast and the in vitro establishment of embryonic stem cell lines. Here, we demonstrate that Foxd3 is also required in the trophoblast lineage. Trophoblast progenitors in Foxd3-/- embryos do not self-renew and are not multipotent, but instead give rise to an excess of trophoblast giant cells. Injection of Foxd3-/- blastocysts with wild type ES cells fails to rescue Foxd3-/- placentas and such chimeras die around 10 days of embryogenesis. These results indicate an essential role for Foxd3 in two nonoverlapping progenitor cell populations that require different secreted factors to maintain their multipotent properties in vitro and give rise to divergent tissues in vivo. Moreover, this provides support for the hypothesis that there are conserved molecular mechanisms for maintaining the self-renewing properties of diverse progenitor cell types.
胚胎成分发育成胎儿并在体外产生胚胎干细胞，而胚外成分发育成胎盘并在体外产生滋养层干细胞。转录抑制因子Foxd3是维持上胚层和体外建立胚胎干细胞系所必需的。在此，我们证明Foxd3在滋养层谱系中也是必需的。Foxd3基因敲除胚胎中的滋养层祖细胞不能自我更新且没有多能性，而是产生过量的滋养层巨细胞。将野生型胚胎干细胞注射到Foxd3基因敲除的囊胚中无法挽救Foxd3基因敲除小鼠的胎盘，此类嵌合体在胚胎发育约10天时死亡。这些结果表明Foxd3在两个不重叠的祖细胞群中起关键作用，这两个祖细胞群在体外需要不同的分泌因子来维持其多能特性，并在体内产生不同的组织。此外，这为存在保守的分子机制来维持不同祖细胞类型的自我更新特性这一假说提供了支持。
