Could the Human Endogenous Retrovirus-Derived Syncytialization Inhibitor, Suppressyn, Limit Heterotypic Cell Fusion Events in the Decidua?

Could the Human Endogenous Retrovirus-Derived Syncytialization Inhibitor, Suppressyn, Limit Heterotypic Cell Fusion Events in the Decidua?
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DOI:
10.3390/ijms221910259
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发表时间:
2021-09-23
影响因子:
5.6
通讯作者:
Schust DJ
Schust DJ
中科院分区:
生物学2区
文献类型:
--
作者:
Sugimoto J;Choi S;Sheridan MA;Koh I;Kudo Y;Schust DJ

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正常的胎盘发育依赖于严格调控的滋养层分化和与母体细胞的相互作用。人内源性逆转录病毒(HERVs)在调节发育中的胎盘滋养层细胞的细胞融合事件中起着不可或缺的作用。合胞素-1(ERVW-1)及其受体、溶质连接载体家族A成员5(SLC 1A 5/ASCT 2)促进细胞滋养层(CTB)细胞融合,产生与母体血液直接接触的多核合胞滋养层(STB)层。另一种被称为Suppressyn(ERVH 48 -1/SUPYN)的HERV衍生蛋白涉及抗融合事件,因为它与ERVW-1共享共同受体。在这里,我们探索原发组织和公开可用的数据集,以确定ERVW-1,ERVH 48 -1和SLC 1A 5表达在母胎界面的分布。SLC 1A 5在胎盘和蜕膜细胞中广泛表达,而ERVW-1和ERVH 48 -1仅限于滋养层细胞。ERVH 48 -1在CTB和绒毛外滋养层中的表达水平高于STB,而ERVW-1通常在STB中最高。我们已经通过基因靶向研究证明,在滋养层细胞/母体子宫内膜细胞相互作用的共培养模型中,suppressyn具有防止ERVW-1诱导的融合事件的能力。这些发现表明,差异HERV表达对于控制胎盘中的融合和抗融合事件至关重要,因此,HERV表达的任何失衡或失调都可能导致不良妊娠结局。
Proper placental development relies on tightly regulated trophoblast differentiation and interaction with maternal cells. Human endogenous retroviruses (HERVs) play an integral role in modulating cell fusion events in the trophoblast cells of the developing placenta. Syncytin-1 (ERVW-1) and its receptor, solute-linked carrier family A member 5 (SLC1A5/ASCT2), promote fusion of cytotrophoblast (CTB) cells to generate the multi-nucleated syncytiotrophoblast (STB) layer which is in direct contact with maternal blood. Another HERV-derived protein known as Suppressyn (ERVH48-1/SUPYN) is implicated in anti-fusogenic events as it shares the common receptor with ERVW-1. Here, we explore primary tissue and publicly available datasets to determine the distribution of ERVW-1, ERVH48-1 and SLC1A5 expression at the maternal-fetal interface. While SLC1A5 is broadly expressed in placental and decidual cell types, ERVW-1 and ERVH48-1 are confined to trophoblast cell types. ERVH48-1 displays higher expression levels in CTB and extravillous trophoblast, than in STB, while ERVW-1 is generally highest in STB. We have demonstrated through gene targeting studies that suppressyn has the ability to prevent ERVW-1-induced fusion events in co-culture models of trophoblast cell/maternal endometrial cell interactions. These findings suggest that differential HERV expression is vital to control fusion and anti-fusogenic events in the placenta and consequently, any imbalance or dysregulation in HERV expression may contribute to adverse pregnancy outcomes.
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