Single cell transcriptomic analysis of human amnion identifies cell-specific signatures associated with membrane rupture and parturition.
Single cell transcriptomic analysis of human amnion identifies cell-specific signatures associated with membrane rupture and parturition.
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DOI：
10.1186/s13578-022-00797-4
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发表时间：
2022-05-18
影响因子：
7.5
通讯作者：
Sun, Kang
中科院分区：
文献类型：
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作者：
Wang, Wang-Sheng;Lin, Yi-Kai;Zhang, Fan;Lei, Wen-Jia;Pan, Fang;Zhu, Ya-Nan;Lu, Jiang-Wen;Zhang, Chu-Yue;Zhou, Qiong;Ying, Hao;Sun, Kang
人的羊膜是一种宫内组织，与分娩的开始有关。深入了解羊膜中单个细胞类型的基因表达特征与分娩时胎膜破裂的关系，可能有助于确定关键的分娩启动因素，以制定预防早产的具体策略，早产是围产儿死亡的主要原因。人羊膜上皮细胞、成纤维细胞和免疫细胞等6种主要细胞类型以及上皮/成纤维细胞、免疫/上皮和免疫/成纤维细胞标记3种细胞类型均表达双重细胞标记。表达这些双重细胞标志物的细胞类型的存在表明羊膜在分娩时存在上皮-间充质(EMT)、上皮-免疫(EIT)和间充质-免疫(MIT)转变。我们发现，羊膜破裂区与分娩时细胞外基质重塑和炎症相关的免疫和EMT细胞亚群比例出现了一些特定的增加。未破裂区与产程中破裂区的上皮细胞和成纤维细胞的亚群组成有一些共同的变化，尤其是与氧化应激、上皮细胞的凋亡和成纤维细胞的锌离子转运有关的变化。此外，我们还发现C-C基序趋化因子配体20(CCL20)是分娩时破裂区羊膜上皮细胞、成纤维细胞和免疫细胞中表达最高的基因之一。对怀孕小鼠的研究表明，注射CCL20会诱导免疫细胞渗入母胎交界处的组织，并导致早产。除了常规的上皮细胞、成纤维细胞和免疫细胞外，人羊膜细胞还可以进行EMT、EIT和FIT，为分娩做准备。破裂区存在强烈的炎症和ECM重塑，而羊膜上皮细胞的凋亡和氧化应激以及成纤维细胞的锌离子转运增强，与分娩时破裂区无关。来源于羊膜主要细胞类型的CCL20参与了临产。网上版载有补充材料，可在10.1186/s13578-022-00797-4查阅。
The human amnion is an intrauterine tissue which is involved in the initiation of parturition. In-depth understanding of gene expression signatures of individual cell types in the amnion with respect to membrane rupture at parturition may help identify crucial initiators of parturition for the development of specific strategies to prevent preterm birth, a leading cause of perinatal mortality. Six major cell types were revealed in human amnion including epithelial cells, fibroblasts and immunocytes as well as three other cell types expressing dual cell markers including epithelial/fibroblast, immune/epithelial and immune/fibroblast markers. The existence of cell types expressing these dual cell markers indicates the presence of epithelial-mesenchymal (EMT), epithelial-immune (EIT) and mesenchymal-immune (MIT) transitions in amnion at parturition. We found that the rupture zone of amnion exhibited some specific increases in subcluster proportions of immune and EMT cells related to extracellular matrix remodeling and inflammation in labor. The non-rupture zone exhibited some common changes in subcluster compositions of epithelial and fibroblast cells with the rupture zone in labor, particularly those related to oxidative stress and apoptosis in epithelial cells and zinc ion transport in fibroblasts. Moreover, we identified that C–C motif chemokine ligand 20 (CCL20) was among the top up-regulated genes in amnion epithelial cells, fibroblasts and immunocytes in the rupture zone at parturition. Studies in pregnant mice showed that administration of CCL20 induced immunocytes infiltration to tissues at the maternal–fetal interface and led to preterm birth. Apart from the conventional epithelial, fibroblast and immunocytes, human amnion cells may undergo EMT, EIT and FIT in preparation for parturition. Intense inflammation and ECM remodeling are present in the rupture zone, while enhanced apoptosis and oxidative stress in epithelial cells and zinc ion transport in fibroblasts are present in amnion regardless of the rupture zones at parturition. CCL20 derived from the major cell types of the amnion participates in labor onset. The online version contains supplementary material available at 10.1186/s13578-022-00797-4.
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影响因子：
2.4
作者：
Bae, Go-Eun;Honga, Joon-Seok;Roh, Cheong-Rae
通讯作者：
Roh, Cheong-Rae
影响因子：
4
作者：
Kagan, HM;Li, WD
通讯作者：
Li, WD
影响因子：
3.9
作者：
Kalinska M;Meyer-Hoffert U;Kantyka T;Potempa J
通讯作者：
Potempa J
影响因子：
3.4
作者：
Gomez-Lopez, N.;Estrada-Gutierrez, G.;Vadillo-Ortega, R.
通讯作者：
Vadillo-Ortega, R.
影响因子：
24.1
作者：
通讯作者：
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