A single-cell atlas of the myometrium in human parturition

Abstract

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.

The single-cell atlas of the murine reproductive tissues during preterm labor

“…Notably, significant agreement was observed for the majority of cell type-specific gene expression changes between the datasets (Figure 8C). The DEGs assigned to the Epithelial-4 and SMC-2 cell types showed only slight agreement between scRNA-seq and bulk datasets (Figure 8C); for the latter subset, this could potentially be explained by the limited capacity of the 10x Genomics technology to encapsulate smooth muscle cells above a specific size threshold, as we have previously reported [71].…”

“…The uterus, decidua, and cervix each displayed a distinct basal (control) cellular repertoire: the uterus showed a predominance of fibroblast (clusters 0 and 1) and non-decidual stromal (clusters 2 and 12) cell types, whereas the decidua also included a unique subset of stromal cells (cluster 4) in addition to the abovementioned cell types (Figure 1I). The uterus and decidua of control mice also included modest populations of innate immune cells such as Monocyte and macrophage subsets as well as lymphocytes such as T cell, NK cell-1, NK cell-2, and B cell (Figure 1I), likely representing the resident immune populations that have been characterized in human and murine tissues [67,69,71,[85][86][87][88]. By contrast with the uterus and decidua, the cervix of control mice comprised a diverse compartment of epithelial subsets (clusters 5,7,8,10,11,14) and other major cell types (Figure 1I), as previously shown [89][90][91].…”

Fetal and maternal NLRP3 signaling is required for preterm labor and birth

“…Uterine activation and contractility. The uterine tissues orchestrate the process of parturition as the transition from a quiescent to a contractile myometrium heralds the onset of labor (Figure 4A), which is accompanied by a surge of proinflammatory mediators (45,46). This inflammatory milieu includes the activation JCI Insight 2022;7(16):e158238 https://doi.org/10.1172/jci.insight.158238 of CASP-1 and release of mature IL-1β (47); however, the contribution of the NLRP3 inflammasome in the uterine tissues has yet to be established.…”

Genetic effects on the timing of parturition and links to fetal birth weight

“…We tested for enrichment based on top loci and genome-wide using partitioned LD-score regression. during labor in single-cells from myometrium 22 . We calculated LD scores (European individuals from phase 3 of the 1000 Genomes project) for sets of genes differentially expressed at labor (± 100 kb) for each cell type separately and for the overall set of genes differentially expressed in the myometrium.…”