Single cell transcriptome analysis of decidua macrophages in normal and recurrent spontaneous abortion patients

Abstract

Due to the heterogeneity and different polarization state of decidual macrophages (dMΦ), they play an important role during the pregnancy, but their definition and exact function remain elusive. We isolated CD14+CD45+ dMΦ from the normal or RSA decidua by flow cytometry, followed by single cell RNA sequencing (scRNA-seq). In total, 23,062 single-cell transcriptomes of macrophage were profiled (12,470 Normal and 10,592 RSA), which were divided into 13 major clusters via T-distributed stochastic neighbor embedding (t-SNE) visualization. We observed that there is higher percentage composition of M1 cells (70.6%) in the normal decidua, and higher percentage composition of M2 cells (68.3%) in the RSA decidua. We identified new markers (M1: S100A8, S100A9, M2: SELENOP, FOLR2, RNASE1) 30 and secreted cytokines (M1: IL1β, TNFSF13B and MMP9; M2: CCL3, CCL4) of the dMΦ. We found that cluster 10 as the specific cluster of dMΦ highly expressing BAG3 in normal group and cluster 7 specific highly expressing CXCL9/10/11 chemokine. After pseudo-time trajectory analysis, we found that the dMΦ formed a continuous "V-shaped" trajectory, with M1 and M2 type cells mainly occupying the two heads. We found that NFκB1, MYC and TCF12 acted as the key transcription factors of dMΦ. Our study redefined the polarization state and physiological characteristic of dMΦ in early normal and RSA pregnancy, which suggests a novel view and therapeutic target for spontaneous abortion prevention.

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis

“…The overall monocyte/macrophage cluster can be identified by expression of CD14, CD16 ( FCGR3A ), CD163, and CD206 ( MRC1 ) ( Fig 6C ). These further subdivided into two subclusters named according to other transcriptional features: Mo/Mφ1 (2,012 cells), which show upregulation of IL1B , CCL20 , CXCL3 , CXCL8 , TNF , EREG , and the inflammasome sensor NLRP3 ; and Mo/Mφ2 (2,919 cells), a reparative phenotype that has been previously reported in non-vascular tissues [ 71 – 73 ]. The latter are characterized by high expression of C1QA/B/C , FOLR2 , HMOX1 , LYVE1 , RNASE1 , SELENOP , and VSIG4 ( Fig 6D and 6E , S5 File in S1 Data ).…”

Single-cell analysis in endometrial research

“…In particular, a decrease in the dNK subset supporting embryonic growth, decrease in the dNK subset (CSF1 + CD59 + KIRs-expressing), decrease in the dNK subset with angiogenic function, increase in the dNK subset characteristic of cytotoxic and immune activation, and increase in the dNK subset (CD56 + CD16 + ) in RPL highlighted the role of dNKs in the pathogenesis of RPL; however, the function of these subsets requires further investigation. Besides dNKs, different macrophage polarization, accumulation of activated dendritic cell sub-population, and abnormal distribution of T cell subtypes were indicated in RPL [52][53][54]86,87] .…”