Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, and Detroit, Michigan, USA.
Department of Obstetrics and Gynecology and.
JCI Insight. 2022 Mar 8;7(5):e153921. doi: 10.1172/jci.insight.153921.
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.
分娩是一个精心协调的过程，其特征是子宫收缩力增加、宫颈成熟和绒毛膜羊膜的激活；然而，从静止的子宫平滑肌向收缩性子宫平滑肌的转变标志着分娩的开始。然而，人类子宫组织中分娩的细胞基础仍知之甚少。在此，我们使用单细胞 RNA 测序 (scRNA-Seq) 对自发性足月分娩的人类子宫进行了全面研究。首先，我们建立了人类子宫的单细胞图谱，并揭示了分娩过程中调节的特定于细胞类型的转录组活性。主要细胞类型包括平滑肌细胞、单核细胞/巨噬细胞、基质细胞和内皮细胞的不同亚群，所有这些细胞都进行了交流，并参与了与分娩相关的免疫（如炎症）和非免疫（如收缩）过程。此外，将 scRNA-Seq 和微阵列数据与批量基因表达的去卷积相结合，突出了平滑肌细胞对与分娩相关的收缩性和炎症过程的贡献。最后，在整个怀孕期间，可以从母体全血转录组中定量检测到源自子宫的单细胞特征，并且在分娩的女性中富集，为非侵入性监测妊娠及其并发症提供了一种潜在的方法。总之，我们的研究结果提供了对特定子宫细胞类型对足月分娩过程中发生的生物学过程的贡献的深入了解。
