A spatially resolved timeline of the human maternal-fetal interface.
A spatially resolved timeline of the human maternal-fetal interface.
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DOI：
10.1038/s41586-023-06298-9
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发表时间：
2023-07
期刊：
影响因子：
64.8
通讯作者：
Angelo, Michael
中科院分区：
文献类型：
--
作者：
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
从孕早期开始，胎儿来源的绒毛外滋养层细胞（EVT）侵入子宫并重塑其螺旋动脉，将其转化为大的扩张血管。已经提出了几种机制来解释EVT如何与母体蜕膜协调，以促进有利于螺旋动脉重塑（SAR）的组织微环境。然而，关于哪些免疫细胞和基质细胞参与这些相互作用以及这种相互作用如何随着胎龄而演变，仍然存在争议。在这里，我们使用了多组学的方法，结合空间蛋白质组学和转录组学的优势，构建一个时空图谱的人类母胎界面在怀孕的前半期。我们使用多路复用离子束成像的飞行时间和37重抗体面板分析约500，000个细胞和588个动脉内完整的蜕膜从66个人之间的6至20周的妊娠，整合此数据集与共注册的转录组学概况。孕龄显著影响母体免疫和基质细胞的频率，表达CD 206、CD 163、TIM-3、半乳糖凝集素-9和IDO-1的致耐受性亚群在稍后的时间点变得越来越富集和共定位。相比之下，SAR进展优先与EVT侵袭相关，并由78个基因本体论途径转录定义，表现出明显的单调和双相趋势。最后，我们开发了一种SAR的综合模型，其中入侵伴随着促血管生成，免疫调节EVT程序，促进与血管内皮细胞的相互作用，同时避免激活母体免疫细胞的上调。一个多组学的方法是用来产生一个时空图集的人类母胎界面在怀孕的前半期，揭示胎龄，绒毛外滋养细胞和螺旋动脉重塑之间的关系。
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). 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 20 weeks 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. A multiomics approach is used to produce a spatiotemporal atlas of the human maternal–fetal interface in the first half of pregnancy, revealing relationships among gestational age, extravillous trophoblasts and spiral artery remodelling.
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影响因子：
46.9
作者：
Greenwald, Noah F.;Miller, Geneva;Moen, Erick;Kong, Alex;Kagel, Adam;Dougherty, Thomas;Fullaway, Christine Camacho;McIntosh, Brianna J.;Leow, Ke Xuan;Schwartz, Morgan Sarah;Pavelchek, Cole;Cui, Sunny;Camplisson, Isabella;Bar-Tal, Omer;Singh, Jaiveer;Fong, Mara;Chaudhry, Gautam;Abraham, Zion;Moseley, Jackson;Warshawsky, Shiri;Soon, Erin;Greenbaum, Shirley;Risom, Tyler;Hollmann, Travis;Bendall, Sean C.;Keren, Leeat;Graf, William;Angelo, Michael;Van Valen, David
通讯作者：
Van Valen, David
影响因子：
7.3
作者：
Gaynor LM;Colucci F
通讯作者：
Colucci F
成像质量细胞仪揭示了髓样细胞在母体界面界面的重要作用。
影响因子：
5.8
作者：
Krop, Juliette;van der Zwan, Anita;Ijsselsteijn, Marieke E.;Kapsenberg, Hanneke;Luk, Sietse J.;Hendriks, Sanne H.;van der Keur, Carin;Verleng, Lotte J.;Somarakis, Antonis;van der Meeren, Lotte;Haasnoot, Geert;Bos, Manon;de Miranda, Noel F. C. C.;Lopes, Susana M. Chuva de Sousa;van der Hoorn, Marie-Louise P.;Koning, Frits;Claas, Frans H. J.;Heidt, Sebastiaan;Eikmans, Michael
通讯作者：
Eikmans, Michael
影响因子：
64.8
作者：
Coorens THH;Oliver TRW;Sanghvi R;Sovio U;Cook E;Vento-Tormo R;Haniffa M;Young MD;Rahbari R;Sebire N;Campbell PJ;Charnock-Jones DS;Smith GCS;Behjati S
通讯作者：
Behjati S
影响因子：
13.6
作者：
Keren, Leeat;Bosse, Marc;Angelo, Michael
通讯作者：
Angelo, Michael