尿囊衍生细胞中的 YAP/TAZ 信号是胎盘血管形成的必要条件

Siqi Gao, Triloshan Thillaikumaran, Martin H Dominguez, William Giang, Kevin Hayes, Xiaowen Chen, Jesse Pace, Jenna Bockman, Danielle Jathan, Derek C Sung, Sweta Narayan, Maxwell Frankfurter, Mei Chen, Patricia Mericko, Jisheng Yang, Marco Castro, Michael Potente, Mark Kahn
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引用次数: 0

摘要

正常的胎盘发育和血管生成对胎儿生长和孕期母体健康至关重要。然而,由于缺乏将胎盘从胚胎和卵黄囊分离出来的特定遗传工具,胎盘血管生成的分子调控一直难以研究。为了填补这一知识空白,我们最近开发了 Hoxa13Cre 小鼠,在这种小鼠中,Cre 在尿囊衍生细胞(包括胎盘内皮细胞和基质细胞)中表达。尿囊衍生细胞中缺乏转录调控因子Yes相关蛋白(YAP)和PDZ结合基序(TAZ)的小鼠在妊娠中期表现出胚胎死亡,胎盘血管受损。 snRNA-seq分析揭示了胎盘基质细胞和内皮细胞的转录变化。YAP/TAZ突变体在内皮结构发生变化之前,胎盘基质细胞明显减少,突出了这些细胞在胎盘血管生长中的作用。这些结果揭示了YAP/TAZ信号在胎盘血管生长过程中的核心作用,并表明Hoxa13衍生的胎盘基质细胞是胎盘血管化的关键组成部分。
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YAP/TAZ signaling in allantois-derived cells is required for placental vascularization
Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed Hoxa13Cre mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells. Mice lacking the transcriptional regulators Yes-associated protein (YAP) and PDZ-binding motif (TAZ) in allantois-derived cells exhibit embryonic lethality at midgestation with compromised placental vasculature. snRNA-seq analysis revealed transcriptional changes in placental stromal cells and endothelial cells. YAP/TAZ mutants exhibited significantly reduced placental stromal cells prior to the endothelial architectural change, highlighting the role of these cells in placental vascular growth. These results reveal a central role for YAP/TAZ signaling during placental vascular growth and implicate Hoxa13-derived placental stromal cells as a critical component of placental vascularization.
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