母体血小板衍生因子诱导滋养细胞LAIR2表达，促进滋养细胞侵袭，抑制胎儿-母体界面血小板活化。

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-03-26 DOI:10.1016/j.jtha.2025.03.020

Freya Lyssy, Désirée Forstner, Jacqueline Guettler, Nadja Kupper, Kaja Ujčič, Lena Neuper, Christine Daxboeck, Amin El-Heliebi, Daniel Kummer, Julian C Krappinger, Djenana Vejzovic, Beate Rinner, Gerhard Cvirn, Stefan Wernitznig, Gerit Moser, Daniela S Valdes, Florian Herse, Anna-Lena Höbler, Juergen Pollheimer, Joanna L James, Julia Feichtinger, Martin Gauster

{"title":"母体血小板衍生因子诱导滋养细胞LAIR2表达，促进滋养细胞侵袭，抑制胎儿-母体界面血小板活化。","authors":"Freya Lyssy, Désirée Forstner, Jacqueline Guettler, Nadja Kupper, Kaja Ujčič, Lena Neuper, Christine Daxboeck, Amin El-Heliebi, Daniel Kummer, Julian C Krappinger, Djenana Vejzovic, Beate Rinner, Gerhard Cvirn, Stefan Wernitznig, Gerit Moser, Daniela S Valdes, Florian Herse, Anna-Lena Höbler, Juergen Pollheimer, Joanna L James, Julia Feichtinger, Martin Gauster","doi":"10.1016/j.jtha.2025.03.020","DOIUrl":null,"url":null,"abstract":"Background: During human placentation extravillous trophoblasts (EVTs), arising from cell column trophoblasts (CCT) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs but their physiological role remained unclear so far.Objective: This study aimed to elucidate the impact of platelet-derived factors on trophoblasts that are exposed to maternal platelets through erosion of decidual blood vessels.Methods: Trophoblast cell line ACH-3P spheroids were incubated either with platelet-derived factors or isolated platelets obtained from pregnant women, and afterwards subjected to RNA sequencing, and validation by qPCR, ELISA and in situ padlock hybridization. Amongst deregulated genes, LAIR2 expression was confirmed in first trimester placenta and primary trophoblast organoids. The functional role of LAIR2 in trophoblast invasion and platelet activation was studied.Results: Platelet-derived factors altered the transcription profile of ACH-3P spheroids, including deregulation of genes linked to embryonic development. Amongst them, LAIR2 was exclusively detected in CCTs and invaded EVTs of first trimester decidua. Histology showed extravasated maternal erythrocytes within interstitial gaps of highly invaded decidua samples, coinciding with LAIR2 positive EVTs. LAIR2 inhibited type 1 collagen -induced platelet activation and enhanced invasiveness of trophoblasts.Conclusion: This study suggests that maternal platelet-derived factors affect the transcription profile of trophoblasts, including upregulation of LAIR2, which may be involved in fine-tuning the coagulation of maternal blood leaking from eroded decidual blood vessels and could increase the invasiveness of EVTs into the decidua through an autocrine mechanism.","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Maternal platelet-derived factors induce trophoblastic LAIR2 expression to promote trophoblast invasion and inhibit platelet activation at the fetal-maternal interface.\",\"authors\":\"Freya Lyssy, Désirée Forstner, Jacqueline Guettler, Nadja Kupper, Kaja Ujčič, Lena Neuper, Christine Daxboeck, Amin El-Heliebi, Daniel Kummer, Julian C Krappinger, Djenana Vejzovic, Beate Rinner, Gerhard Cvirn, Stefan Wernitznig, Gerit Moser, Daniela S Valdes, Florian Herse, Anna-Lena Höbler, Juergen Pollheimer, Joanna L James, Julia Feichtinger, Martin Gauster\",\"doi\":\"10.1016/j.jtha.2025.03.020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: During human placentation extravillous trophoblasts (EVTs), arising from cell column trophoblasts (CCT) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs but their physiological role remained unclear so far.Objective: This study aimed to elucidate the impact of platelet-derived factors on trophoblasts that are exposed to maternal platelets through erosion of decidual blood vessels.Methods: Trophoblast cell line ACH-3P spheroids were incubated either with platelet-derived factors or isolated platelets obtained from pregnant women, and afterwards subjected to RNA sequencing, and validation by qPCR, ELISA and in situ padlock hybridization. Amongst deregulated genes, LAIR2 expression was confirmed in first trimester placenta and primary trophoblast organoids. The functional role of LAIR2 in trophoblast invasion and platelet activation was studied.Results: Platelet-derived factors altered the transcription profile of ACH-3P spheroids, including deregulation of genes linked to embryonic development. Amongst them, LAIR2 was exclusively detected in CCTs and invaded EVTs of first trimester decidua. Histology showed extravasated maternal erythrocytes within interstitial gaps of highly invaded decidua samples, coinciding with LAIR2 positive EVTs. LAIR2 inhibited type 1 collagen -induced platelet activation and enhanced invasiveness of trophoblasts.Conclusion: This study suggests that maternal platelet-derived factors affect the transcription profile of trophoblasts, including upregulation of LAIR2, which may be involved in fine-tuning the coagulation of maternal blood leaking from eroded decidual blood vessels and could increase the invasiveness of EVTs into the decidua through an autocrine mechanism.\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-03-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2025.03.020\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2025.03.020","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：在人胎盘过程中，由细胞柱滋养细胞（CCT）产生的外膜滋养细胞（EVTs）侵入高度分化的子宫粘膜，称为蜕膜，在那里它们侵蚀血管并取代血管内皮细胞。母体血小板存在于cct细胞间隙中，但其生理作用尚不清楚。目的：本研究旨在阐明血小板衍生因子对滋养细胞的影响，滋养细胞暴露于母体血小板通过侵蚀蜕膜血管。方法：将滋养细胞ACH-3P球体与孕妇血小板源性因子或分离血小板孵育，进行RNA测序，qPCR、ELISA和原位挂锁杂交验证。在不受调控的基因中，LAIR2的表达在妊娠早期胎盘和初级滋养细胞类器官中得到证实。研究了LAIR2在滋养细胞侵袭和血小板活化中的功能作用。结果：血小板来源的因子改变了ACH-3P球体的转录谱，包括与胚胎发育相关的基因的失调。其中LAIR2仅在早期妊娠蜕膜的cct和侵袭evt中检测到。组织学显示高度侵润的蜕膜标本间质间隙外渗母体红细胞，与LAIR2阳性evt一致。LAIR2抑制1型胶原诱导的血小板活化，增强滋养层细胞的侵袭性。结论：本研究提示母体血小板源性因子影响滋养细胞的转录谱，包括LAIR2的上调，这可能参与了母体血液从侵蚀的蜕膜血管渗漏的凝固微调，并可能通过自分泌机制增加evt对蜕膜的侵袭性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Maternal platelet-derived factors induce trophoblastic LAIR2 expression to promote trophoblast invasion and inhibit platelet activation at the fetal-maternal interface.

Background: During human placentation extravillous trophoblasts (EVTs), arising from cell column trophoblasts (CCT) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs but their physiological role remained unclear so far.

Objective: This study aimed to elucidate the impact of platelet-derived factors on trophoblasts that are exposed to maternal platelets through erosion of decidual blood vessels.

Methods: Trophoblast cell line ACH-3P spheroids were incubated either with platelet-derived factors or isolated platelets obtained from pregnant women, and afterwards subjected to RNA sequencing, and validation by qPCR, ELISA and in situ padlock hybridization. Amongst deregulated genes, LAIR2 expression was confirmed in first trimester placenta and primary trophoblast organoids. The functional role of LAIR2 in trophoblast invasion and platelet activation was studied.

Results: Platelet-derived factors altered the transcription profile of ACH-3P spheroids, including deregulation of genes linked to embryonic development. Amongst them, LAIR2 was exclusively detected in CCTs and invaded EVTs of first trimester decidua. Histology showed extravasated maternal erythrocytes within interstitial gaps of highly invaded decidua samples, coinciding with LAIR2 positive EVTs. LAIR2 inhibited type 1 collagen -induced platelet activation and enhanced invasiveness of trophoblasts.

Conclusion: This study suggests that maternal platelet-derived factors affect the transcription profile of trophoblasts, including upregulation of LAIR2, which may be involved in fine-tuning the coagulation of maternal blood leaking from eroded decidual blood vessels and could increase the invasiveness of EVTs into the decidua through an autocrine mechanism.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.