Expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 at single cell resolution in the peripartum decidua.

Angiotensin-converting enzyme 2 (ACE2) is the key receptor for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, the susceptibility of the decidua to infection during the peripartum period has not been explored, even though this may affect vertical transmission. The objective of this study was to investigate the expression of ACE2 and related genes in the decidua during delivery. Here, single-cell RNA sequencing was used to characterize the transcriptomes of decidual cells before and after the onset of labor. During the peripartum period, ACE2 expression was highly heterogeneous. ACE2 was expressed principally in decidual stromal cells, uterine smooth muscle cells, and extravillous trophoblasts. Comparison of the transcriptomes of ACE2-positive and ACE2-negative cells indicated that ACE2-positive cells exhibited integrin clusters on the cell surface interactions. ACE2-positive cells were compared before and after labor onset. After delivery, the number of ACE2-positive cells was slightly higher than before delivery. Before labor onset, ACE2-positive decidual stromal cells were in the regulation of membrane protein ectodomain proteolysis cluster. After labor onset, the upregulated genes changed to include cell junction assembly genes. The susceptibility of decidual cells to SARS-CoV-2 infection is thus heterogeneous during the peripartum period.

Single-cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period.

OBJECTIVES: The decidua is a tissue that contacts both maternal and foetal components and is pivotal to labour onset due to its location. Due to the heterogeneity of decidual tissue, it is challenging to study its role in the peripartum period. Herein, we analysed the transcriptomes of peripartum decidua at single-cell resolution. MATERIALS AND METHODS: Single-cell RNA sequencing was performed for 29 231 decidual cells before and after delivery to characterize the transcriptomes. RESULTS: Eight major cell types (including endothelial cells, fibroblasts) and subtypes of decidual stromal cells, extravillous trophoblasts and T cells were identified and found to have various functions. Compared with before delivery, the activation of decidual stromal cell, extravillous trophoblast and T-cell subtypes to different degrees was observed after delivery. Furthermore, the activation involved multiple functions, such as cell proliferation, and several pathways, such as the activator protein 1 pathway. The results of pseudotemporal ordering showed differentiation of decidual stromal cell and extravillous trophoblast subtypes, suggesting inhomogeneity of these subgroups in decidualization (decidual stromal cell) and invasion (extravillous trophoblast). CONCLUSIONS: The peripartum decidual tissue is heterogeneous. This study revealed changes in the decidua and its components at single-cell resolution; these findings provide a new perspective for the study of peripartum decidua.

Single-cell transcriptomics analysis showing functional heterogeneity in decidual stromal cells during labor.

To investigate the heterogeneity of decidual stromal cells (DSCs) and their functional alterations during delivery, we conducted single-cell RNA sequencing analysis to characterize the transcriptomic profiles of DSCs before and after labor onset. According to their transcriptomic profiles, DSCs (6382 cells) were clustered into five subgroups with different functions. Similar to stromal cells, cells in cluster 1 were involved in cell substrate adhesion. On the other hand, cells in clusters 2 and 3 were enriched in signal transduction-related genes. Labor onset led to significant alterations in many pathways, including the activator protein 1 pathway (all clusters), as well as in the response to lipopolysaccharide (clusters 1-3). The downregulated genes were involved in coagulation, ATP synthesis, and oxygen homeostasis, possibly reflecting the oxygen and energy balance during delivery. Our findings highlight that peripartum DSCs are heterogeneous and play multiple roles in labor.