Spatial multiomics map of trophoblast development in early pregnancy.

Spatial multiomics map of trophoblast development in early pregnancy.
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DOI:
10.1038/s41586-023-05869-0
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发表时间:
2023-04
期刊:
影响因子:
64.8
通讯作者:
Vento-Tormo, Roser
Vento-Tormo, Roser
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arutyunyan, Anna;Roberts, Kenny;Troule, Kevin;Wong, Frederick C. K.;Sheridan, Megan A. A.;Kats, Ilia;Garcia-Alonso, Luz;Velten, Britta;Hoo, Regina;Ruiz-Morales, Elias R. R.;Sancho-Serra, Carmen;Shilts, Jarrod;Handfield, Louis-Francois;Marconato, Luca;Tuck, Elizabeth;Gardner, Lucy;Mazzeo, Cecilia Icoresi;Li, Qian;Kelava, Iva;Wright, Gavin J. J.;Prigmore, Elena;Teichmann, Sarah A. A.;Bayraktar, Omer Ali;Moffett, Ashley;Stegle, Oliver;Turco, Margherita Y. Y.;Vento-Tormo, Roser

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人类胎盘(胎儿形成的胚胎外器官)与蜕膜(子宫粘膜层)之间的关系对于怀孕期间滋养和保护胎儿至关重要。来自胎盘绒毛的绒毛外滋养层细胞 (EVT) 浸润蜕膜,将母体动脉转化为高电导血管。妊娠早期建立的滋养层侵袭和动脉转化缺陷是常见妊娠疾病(例如先兆子痫)的基础。在这里,我们生成了整个人类母胎界面(包括子宫肌层)的空间解析多组学单细胞图谱,这使我们能够解析滋养层分化的完整轨迹。我们使用该细胞图谱来推断介导 EVT 侵袭的可能转录因子,并表明它们保留在从初级滋养层类器官和滋养层干细胞分化的 EVT 体外模型中。我们定义了滋养层侵袭的最终细胞状态的转录组:胎盘床巨细胞(融合的多核 EVT)和血管内 EVT(在母体动脉内形成栓塞)。我们预测了导致滋养层侵袭和胎盘床巨细胞形成的细胞间通讯事件,并模拟了间质 EVT 和血管内 EVT 在介导妊娠早期动脉转化中的双重作用。总之,我们的数据提供了对植入后滋养层分化的全面分析,可用于为妊娠早期人类胎盘实验模型的设计提供信息。包括子宫肌层在内的人类母胎界面的多组学单细胞图谱,将空间转录组学数据与染色质可及性相结合,提供了妊娠早期胎盘细胞浸润子宫时细胞状态的全面分析。
The relationship between the human placenta—the extraembryonic organ made by the fetus, and the decidua—the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia. Here we have generated a spatially resolved multiomics single-cell atlas of the entire human maternal–fetal interface including the myometrium, which enables us to resolve the full trajectory of trophoblast differentiation. We have used this cellular map to infer the possible transcription factors mediating EVT invasion and show that they are preserved in in vitro models of EVT differentiation from primary trophoblast organoids and trophoblast stem cells. We define the transcriptomes of the final cell states of trophoblast invasion: placental bed giant cells (fused multinucleated EVTs) and endovascular EVTs (which form plugs inside the maternal arteries). We predict the cell–cell communication events contributing to trophoblast invasion and placental bed giant cell formation, and model the dual role of interstitial EVTs and endovascular EVTs in mediating arterial transformation during early pregnancy. Together, our data provide a comprehensive analysis of postimplantation trophoblast differentiation that can be used to inform the design of experimental models of the human placenta in early pregnancy. A multiomics single-cell atlas of the human maternal–fetal interface including the myometrium, combining spatial transcriptomics data with chromatin accessibility, provides a comprehensive analysis of cell states as placental cells infiltrate the uterus during early pregnancy.
DOI: 10.1073/pnas.1706546114
发表时间: 2017-10-03
影响因子: 11.1
作者:
Garrido-Gomez, Tamara;Dominguez, Francisco;Simon, Carlos
通讯作者: Simon, Carlos
DOI: 10.1016/s0002-9440(10)64849-3
发表时间: 2000-12-01
影响因子: 6
作者:
Jauniaux, E;Watson, AL;Burton, GJ
通讯作者: Burton, GJ
DOI: 10.1016/j.molcel.2010.05.004
发表时间: 2010-05-28
期刊: Molecular cell
影响因子: 16
作者:
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者: Glass CK
DOI: 10.1038/s41596-020-0292-x
发表时间: 2020-02-26
期刊: NATURE PROTOCOLS
影响因子: 14.8
作者:
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者: Vento-Tormo, Roser
DOI: 10.1016/j.placenta.2017.06.007
发表时间: 2017-12-01
期刊: PLACENTA
影响因子: 3.8
作者:
Burton, Graham J.;Jauniaux, Eric
通讯作者: Jauniaux, Eric