Abstract:
The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell-cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development.
摘要:
人脐带(hUC)是连接胎儿与母亲的生命线。hUC的高螺旋与产前和围产期发病率和死亡率有关。我们使用最先进的成像和组学方法研究了hUC超卷的起源。对hUC的宏观检查显示,螺旋起源于动脉,而不是hUC的其他成分。hUC动脉的数字重建显示,中膜中两层肌纤维的动态排列方向相反。我们观察到基因同卵双胞胎可能对hUC盘绕不一致,排除遗传,许多环境,和hUC卷绕的父母起源。比较四对双生子的hUC动脉的转录组和DNA甲基化谱,我们检测到28个差异表达基因,但没有差异甲基化的CpG.这些基因在血管发育中起作用,细胞-细胞相互作用,和轴的形成,并可能导致hUC螺旋数量的增加。当组合时,我们的研究结果为理解胎儿发育中hUC螺旋的起源提供了一个新的框架.