Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5.
Dev Biol. 2022 Mar;483:22-33. doi: 10.1016/j.ydbio.2021.12.014. Epub 2021 Dec 30.
The extra-embryonic yolk sac contains adjacent layers of mesoderm and visceral endoderm. The mesodermal layer serves as the first site of embryonic hematopoiesis, while the visceral endoderm provides a means of exchanging nutrients and waste until the development of the chorioallantoic placenta. While defects in chorioallantoic fusion and yolk sac hematopoiesis have been described in Cdx mutant mouse models, little is known about the gene targets and molecular mechanisms through which Cdx members regulate these processes. To this end, we used RNA-seq to examine Cdx-dependent gene expression changes in the yolk sac. We find that loss of Cdx function impacts the expression of genes involved in yolk sac hematopoiesis, as previously described, as well as novel Cdx2 target genes. In addition, we observed Cdx-dependent changes in PRC2 subunit expression accompanied by altered H3K27me3 deposition at a subset of Cdx target genes as early as E7.5 in the embryo proper. This study identifies additional Cdx target genes and provides further evidence for Cdx-dependent epigenetic regulation of gene expression in the early embryo, and that this regulation is required to maintain gene expression programs in the extra-embryonic yolk sac at later developmental stages.
胚外卵黄囊包含相邻的中胚层和内胚层。中胚层作为胚胎造血的第一个部位，而内胚层提供了一种交换营养物质和废物的方式，直到绒毛尿囊胎盘的发育。虽然在 Cdx 突变体小鼠模型中已经描述了绒毛尿囊融合和卵黄囊造血的缺陷，但对于 Cdx 成员调节这些过程的基因靶点和分子机制知之甚少。为此，我们使用 RNA-seq 检查了卵黄囊中与 Cdx 相关的基因表达变化。我们发现 Cdx 功能的丧失会影响卵黄囊造血相关基因的表达，正如之前所描述的那样，以及新的 Cdx2 靶基因。此外，我们观察到 PRC2 亚基表达的 Cdx 依赖性变化，伴随着胚胎适当的 E7.5 时在一组 Cdx 靶基因上的 H3K27me3 沉积的改变。这项研究确定了其他的 Cdx 靶基因，并为早期胚胎中 Cdx 依赖的表观遗传调控基因表达提供了进一步的证据，并且这种调控对于维持胚胎外卵黄囊中基因表达程序在后期发育阶段是必需的。
