Single cell transcriptional signatures of the human placenta in term and preterm parturition
Single cell transcriptional signatures of the human placenta in term and preterm parturition
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DOI：
10.7554/elife.52004
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发表时间：
2019-12-12
期刊：
影响因子：
7.7
通讯作者：
Gomez-Lopez, Nardhy
中科院分区：
文献类型：
--
作者：
Pique-Regi, Roger;Romero, Roberto;Gomez-Lopez, Nardhy
每年有超过1.35亿人出生；然而，人类分娩在妊娠组织中的分子基础，特别是胎盘，仍然知之甚少。胎盘是一个复杂的异质器官，包括来自母体和胎儿的细胞，破坏母胎对话可能导致不良妊娠结局，如早产。在生理性和病理性分娩过程中，对胎盘及其室的细胞类型组成和转录活性的了解有限。为了填补这一知识空白，我们使用scRNA-seq分析了足月分娩或未足月分娩和早产妇女的胎盘绒毛树、基板和绒毛膜。在胎盘室和研究组之间，细胞类型组成和转录谱存在显著差异。首次发现两种细胞类型：1)绒毛膜中的淋巴内皮蜕膜细胞和2)胎盘绒毛中的非增殖性间质细胞滋养细胞。来自绒毛膜和羊膜的母体巨噬细胞在两个分娩过程中表现出最大的基因表达差异（如NFKB1）；然而，在早产中也检测到特定的基因表达变化。重要的是，在母体循环中，几个胎盘scRNA-seq转录特征随着妊娠的推进而被调节，特异性免疫细胞类型特征随着足月分娩（nk细胞和活化t细胞特征）和早产（巨噬细胞、单核细胞和活化t细胞特征）而增加。在此，我们提供了人类胎盘细胞类型和转录谱的目录，揭示了生理性和病理性分娩的分子基础和非侵入性预测。
More than 135 million births occur each year; yet, the molecular underpinnings of human parturition in gestational tissues, and in particular the placenta, are still poorly understood. The placenta is a complex heterogeneous organ including cells of both maternal and fetal origin, and insults that disrupt the maternal-fetal dialogue could result in adverse pregnancy outcomes such as preterm birth. There is limited knowledge of the cell type composition and transcriptional activity of the placenta and its compartments during physiologic and pathologic parturition. To fill this knowledge gap, we used scRNA-seq to profile the placental villous tree, basal plate, and chorioamniotic membranes of women with or without labor at term and those with preterm labor. Significant differences in cell type composition and transcriptional profiles were found among placental compartments and across study groups. For the first time, two cell types were identified: 1) lymphatic endothelial decidual cells in the chorioamniotic membranes, and 2) non-proliferative interstitial cytotrophoblasts in the placental villi. Maternal macrophages from the chorioamniotic membranes displayed the largest differences in gene expression (e.g. NFKB1) in both processes of labor; yet, specific gene expression changes were also detected in preterm labor. Importantly, several placental scRNA-seq transcriptional signatures were modulated with advancing gestation in the maternal circulation, and specific immune cell type signatures were increased with labor at term (NK-cell and activated T-cell signatures) and with preterm labor (macrophage, monocyte, and activated T-cell signatures). Herein, we provide a catalogue of cell types and transcriptional profiles in the human placenta, shedding light on the molecular underpinnings and non-invasive prediction of the physiologic and pathologic parturition.