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A single-cell atlas of the myometrium in human parturition
Roger Pique-Regi, Roberto Romero, Valeria Garcia-Flores, Azam Peyvandipour, Adi L. Tarca, Errile Pusod, Jose Galaz, Derek Miller, Gaurav Bhatti, Robert Para, Tomi Kanninen, Ola Hadaya, Carmen Paredes, Kenichiro Motomura, Jeffrey R. Johnson, Eunjung Jung, Chaur-Dong Hsu, Stanley M. Berry, Nardhy Gomez-Lopez
Roger Pique-Regi, Roberto Romero, Valeria Garcia-Flores, Azam Peyvandipour, Adi L. Tarca, Errile Pusod, Jose Galaz, Derek Miller, Gaurav Bhatti, Robert Para, Tomi Kanninen, Ola Hadaya, Carmen Paredes, Kenichiro Motomura, Jeffrey R. Johnson, Eunjung Jung, Chaur-Dong Hsu, Stanley M. Berry, Nardhy Gomez-Lopez
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Research Article Cell biology Reproductive biology

A single-cell atlas of the myometrium in human parturition

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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.

Authors

Roger Pique-Regi, Roberto Romero, Valeria Garcia-Flores, Azam Peyvandipour, Adi L. Tarca, Errile Pusod, Jose Galaz, Derek Miller, Gaurav Bhatti, Robert Para, Tomi Kanninen, Ola Hadaya, Carmen Paredes, Kenichiro Motomura, Jeffrey R. Johnson, Eunjung Jung, Chaur-Dong Hsu, Stanley M. Berry, Nardhy Gomez-Lopez

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Figure 4

The myometrial transcriptomic profile in labor.

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The myometrial transcriptomic profile in labor.
(A) Diagram illustrating...
(A) Diagram illustrating the common pathway of labor. (B) Uniform manifold approximation and projection (UMAP) plot showing cell clusters in the myometrial tissues from women in labor (n = 11, red) and not in labor (n = 13, blue). (C) Bar plots showing the number of cells for each cell type in the myometrial tissues from women in labor (red) and not in labor (blue). The comparison of the numbers of each cell type between the 2 study groups was performed using a 2-sided binomial test where q < 0.05 is considered significant, as represented by an asterisk (*). (D) ClusterProfiler dot plot showing the Gene Ontology (GO) biological processes that are enriched in labor based on differentially expressed genes (DEGs) in the SMC-1 cell type (q < 0.1), where the size and color of the dots represent enrichment score and significance level, respectively. The overrepresentation analysis was performed based on the 1-sided Fisher’s exact test (ClusterProfiler). GO terms with q < 0.1 were selected. Highlighted in orange are pathways associated with uterine contractility. (E) Bar plot showing the number of labor-associated DEGs for each cell type, where red and blue indicate upregulated and downregulated DEGs, respectively. The comparison between upregulated and downregulated DEGs was calculated using a 2-sided binomial test, where q < 0.05 is considered significant. *q < 0.05, **q < 0.01, ****q < 0.0001. (F) Quantile-quantile plot showing differential expression of genes analyzed for selected enriched cell types from the myometrial tissues. Deviation above the 1:1 line (solid black line) indicates enrichment. DC, dendritic cell; EVT, extravillous trophoblast; ILC, innate lymphoid cell; LED, lymphoid endothelial decidual cell; NK cell, natural killer cell; SMC, smooth muscle cell.

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ISSN 2379-3708

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