美国斯坦福大学Michael Angelo等研究人员合作揭示人类母胎界面的空间分辨时间轴。2023年7月19日，《自然》杂志在线发表了这项成果。
研究人员采用多组学方法，并结合空间蛋白质组学和转录组学的优势，构建了妊娠前半期人类母胎界面的时空图谱。研究人员利用飞行时间多路离子束成像技术和 37 复合物抗体面板分析了妊娠 6 至 20 周期间 66 人完整蜕膜中的约 50 万个细胞和 588 条动脉，并将此数据集与共采集的转录组学图谱整合在一起。妊娠年龄极大地影响了母体免疫细胞和基质细胞的频率，表达CD206、CD163、TIM-3、galectin-9和IDO-1的耐受性亚群在较晚的时间点变得越来越富集和共定位。
相比之下，螺旋动脉重塑（SAR）的进展与EVT的入侵有优先相关性，并由78个基因本体通路转录定义，表现出不同的单调和双相趋势。最后，研究人员建立了一个 SAR 综合模型，在该模型中，伴随入侵的是促血管生成、免疫调节体外滋养细胞（EVT）程序的上调，这些程序可促进与血管内皮的相互作用，同时避免激活母体免疫细胞。
据介绍，从妊娠头三个月开始，胎儿衍生的EVT侵入子宫并重塑其螺旋动脉，将其转化为扩张的大血管。有几种机制可以解释EVT如何与母体蜕膜协调，进而促进有利于SAR的组织微环境。然而，关于哪些免疫细胞和基质细胞参与了这些相互作用，以及这种相互作用如何随孕龄变化而变化，目前仍存在争议。
附：英文原文
Title: A spatially resolved timeline of the human maternal–fetal interface
Author: Greenbaum, Shirley, Averbukh, Inna, Soon, Erin, Rizzuto, Gabrielle, Baranski, Alex, Greenwald, Noah F., Kagel, Adam, Bosse, Marc, Jaswa, Eleni G., Khair, Zumana, Kwok, Shirley, Warshawsky, Shiri, Piyadasa, Hadeesha, Goldston, Mako, Spence, Angie, Miller, Geneva, Schwartz, Morgan, Graf, Will, Van Valen, David, Winn, Virginia D., Hollmann, Travis, Keren, Leeat, van de Rijn, Matt, Angelo, Michael
Issue&Volume: 2023-07-19
Abstract: Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)1,2,3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal–fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.
DOI: 10.1038/s41586-023-06298-9
Source: https://www.nature.com/articles/s41586-023-06298-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
