Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA; Institute for Reproductive Health and Regenerative Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Placenta. 2017 Dec;60 Suppl 1(Suppl 1):S61-S66. doi: 10.1016/j.placenta.2017.05.005. Epub 2017 May 10.
Mammalian reproduction is critically dependent on trophoblast cells, which ensure embryo implantation and placentation. Development of trophoblast cell lineages is a multi-step process and relies upon proper spatial and temporal gene expression, which is regulated by multiple transcription factors. However, most of the transcription factors that are implicated in trophoblast development regulate gene expression at a specific developmental stage or in a specific trophoblast subtype. In contrast, recent studies from our group and other laboratories indicate that conserved GATA family of transcription factors, GATA2 and GATA3, are important to regulate gene expression at multiple stages of trophoblast development. Furthermore, our conditional gene deletion studies revealed that functional redundancy of GATA2 and GATA3 ensures both self-renewal of trophoblast stem and progenitor cells and their differentiation to trophoblast cells of a matured placenta. Together these findings indicate that GATA2/GATA3 are the master orchestrators of gene expression in trophoblast cells and they fine tune gene regulatory network to establish distinct trophoblast cell types during placentation.
哺乳动物的繁殖过程严重依赖滋养层细胞，滋养层细胞可确保胚胎着床和胎盘形成。滋养层细胞谱系的发育是一个多步骤的过程，依赖于适当的时空基因表达，而时空基因表达又受到多个转录因子的调控。然而，大多数参与滋养层细胞发育的转录因子在特定的发育阶段或特定的滋养层亚型中调节基因表达。相比之下，我们小组和其他实验室的最近研究表明，保守的 GATA 转录因子家族成员 GATA2 和 GATA3 对于调节滋养层细胞发育的多个阶段的基因表达至关重要。此外，我们的条件性基因缺失研究表明，GATA2 和 GATA3 的功能冗余确保了滋养层干细胞和祖细胞的自我更新及其向成熟胎盘滋养层细胞的分化。这些发现共同表明，GATA2/GATA3 是滋养层细胞中基因表达的主要调控因子，它们通过微调基因调控网络，在胎盘形成过程中建立不同的滋养层细胞类型。
