Pregnancy 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, MD 20892 and Detroit, MI 48201, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Sci Transl Med. 2024 Jan 10;16(729):eadh8335. doi: 10.1126/scitranslmed.adh8335.
Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal cross-talk in labor have not been fully elucidated. Here, single-cell RNA sequencing (scRNA-seq) was applied to decipher maternal-fetal signaling in the human placenta during term labor. First, a single-cell atlas of the human placenta was established, demonstrating that maternal and fetal cell types underwent changes in transcriptomic activity during labor. Cell types most affected by labor were fetal stromal and maternal decidual cells in the chorioamniotic membranes (CAMs) and maternal and fetal myeloid cells in the placenta. Cell-cell interaction analyses showed that CAM and placental cell types participated in labor-driven maternal and fetal signaling, including the collagen, C-X-C motif ligand (CXCL), tumor necrosis factor (TNF), galectin, and interleukin-6 (IL-6) pathways. Integration of scRNA-seq data with publicly available bulk transcriptomic data showed that placenta-derived scRNA-seq signatures could be monitored in the maternal circulation throughout gestation and in labor. Moreover, comparative analysis revealed that placenta-derived signatures in term labor were mirrored by those in spontaneous preterm labor and birth. Furthermore, we demonstrated that early in gestation, labor-specific, placenta-derived signatures could be detected in the circulation of women destined to undergo spontaneous preterm birth, with either intact or prelabor ruptured membranes. Collectively, our findings provide insight into the maternal-fetal cross-talk of human parturition and suggest that placenta-derived single-cell signatures can aid in the development of noninvasive biomarkers for the prediction of preterm birth.
分娩是一个复杂的生理过程，需要母亲和胎儿之间进行良好的协调对话。然而，促进分娩时母婴对话的细胞贡献和通讯尚未完全阐明。在这里，我们应用单细胞 RNA 测序（scRNA-seq）来解析足月分娩时人胎盘内的母婴信号。首先，我们建立了人胎盘的单细胞图谱，表明母胎细胞类型在分娩过程中转录组活性发生了变化。受分娩影响最大的细胞类型是绒毛膜羊膜（CAM）中的胎儿基质细胞和母体蜕膜细胞，以及胎盘中的母胎髓样细胞。细胞间相互作用分析表明，CAM 和胎盘细胞类型参与了分娩驱动的母婴信号传递，包括胶原、C-X-C 基序配体（CXCL）、肿瘤坏死因子（TNF）、半乳糖凝集素和白细胞介素 6（IL-6）途径。将 scRNA-seq 数据与公开的批量转录组数据整合表明，胎盘衍生的 scRNA-seq 特征可以在整个妊娠期间和分娩时在母体循环中监测到。此外，比较分析表明，足月分娩时胎盘衍生的特征与自发性早产和分娩时的特征相似。此外，我们证明在妊娠早期，在自发性早产的女性循环中，可以检测到与分娩相关的胎盘衍生特征，这些女性的胎膜完整或未足月破裂。总之，我们的发现提供了对人类分娩时母婴对话的深入了解，并表明胎盘衍生的单细胞特征可以帮助开发非侵入性生物标志物来预测早产。
