A single-cell atlas of the myometrium in human parturition.
A single-cell atlas of the myometrium in human parturition.
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DOI：
10.1172/jci.insight.153921
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发表时间：
2022-03-08
期刊：
影响因子：
8
通讯作者：
Gomez-Lopez N
中科院分区：
文献类型：
--
作者：
Pique-Regi R;Romero R;Garcia-Flores V;Peyvandipour A;Tarca AL;Pusod E;Galaz J;Miller D;Bhatti G;Para R;Kanninen T;Hadaya O;Paredes C;Motomura K;Johnson JR;Jung E;Hsu CD;Berry SM;Gomez-Lopez N
分娩是一个精心安排的过程，其特征是子宫收缩增强、宫颈成熟和绒毛羊膜激活；然而，从静止的子宫肌层到收缩的肌层的转变预示着分娩的开始。然而，人类分娩在子宫组织中的细胞基础仍然知之甚少。在此，我们使用单细胞RNA测序(scRNA-Seq)对自然足月分娩期间的人子宫肌层进行了全面的研究。首先，我们建立了人类子宫肌层的单细胞图谱，并解开了在分娩过程中调节的特定细胞类型的转录活动。主要细胞类型包括平滑肌细胞、单核/巨噬细胞、基质细胞和内皮细胞的不同亚群，所有这些细胞都沟通和参与与分娩相关的免疫(例如炎症)和非免疫(例如收缩)过程。此外，将scRNA-Seq和微阵列数据与大宗基因表达的去卷积结合起来，突出了平滑肌细胞对劳动相关收缩和炎症过程的贡献。最后，子宫肌层衍生的单细胞信号可以在整个怀孕期间在母亲的全血转录组中定量，并在分娩中的妇女中得到丰富，为非侵入性监测怀孕及其并发症提供了一种潜在的手段。总之，我们的发现提供了对特定的子宫肌层细胞类型在足月分娩期间发生的生物学过程中的贡献的洞察力。
Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type–specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.