Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Integrative Bioinformatics Supportive Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Biol Reprod. 2022 Aug 9;107(2):529-545. doi: 10.1093/biolre/ioac061.
Uterine dysfunctions lead to fertility disorders and pregnancy complications. Normal uterine functions at pregnancy depend on crosstalk among multiple cell types in uterine microenvironments. Here, we performed the spatial transcriptomics and single-cell RNA-seq assays to determine local gene expression profiles at the embryo implantation site of the mouse uterus on pregnancy day 7.5 (D7.5). The spatial transcriptomic annotation identified 11 domains of distinct gene signatures, including a mesometrial myometrium, an anti-mesometrial myometrium, a mesometrial decidua enriched with natural killer cells, a vascular sinus zone for maternal vessel remodeling, a fetal-maternal interface, a primary decidual zone, a transition decidual zone, a secondary decidual zone, undifferentiated stroma, uterine glands, and the embryo. The scRNA-Seq identified 12 types of cells in the D7.5 uterus including three types of stromal fibroblasts with differentiated and undifferentiated markers, one cluster of epithelium including luminal and glandular epithelium, mesothelium, endothelia, pericytes, myelomonocytic cell, natural killer cells, and lymphocyte B. These single-cell RNA signatures were then utilized to deconvolute the cell-type compositions of each individual uterine microenvironment. Functional annotation assays on spatial transcriptomic data revealed uterine microenvironments with distinguished metabolic preferences, immune responses, and various cellular behaviors that are regulated by region-specific endocrine and paracrine signals. Global interactome among regions is also projected based on the spatial transcriptomic data. This study provides high-resolution transcriptome profiles with locality information at the embryo implantation site to facilitate further investigations on molecular mechanisms for normal pregnancy progression.
子宫功能障碍导致生育障碍和妊娠并发症。妊娠时正常的子宫功能依赖于子宫微环境中多种细胞类型的串扰。在这里，我们对妊娠第 7.5 天（D7.5）的小鼠子宫胚胎着床部位进行了空间转录组学和单细胞 RNA-seq 分析，以确定局部基因表达谱。空间转录组注释鉴定了 11 个具有独特基因特征的区域，包括中隔肌层、反中隔肌层、富含自然杀伤细胞的中隔蜕膜、用于母体血管重塑的血管窦区、胎儿-母体界面、初级蜕膜区、过渡蜕膜区、次级蜕膜区、未分化基质、子宫腺和胚胎。单细胞 RNA-seq 在 D7.5 子宫中鉴定出 12 种细胞类型，包括三种具有分化和未分化标记的基质成纤维细胞，一种上皮细胞簇，包括腔上皮和腺上皮、间皮、内皮细胞、周细胞、髓样单核细胞、自然杀伤细胞和淋巴细胞 B。然后，这些单细胞 RNA 特征被用于解析每个子宫微环境的细胞类型组成。对空间转录组数据的功能注释分析揭示了具有独特代谢偏好、免疫反应和各种细胞行为的子宫微环境，这些行为受区域特异性内分泌和旁分泌信号的调节。还基于空间转录组数据预测了区域间的全局相互作用组。这项研究提供了具有局部信息的胚胎着床部位的高分辨率转录组图谱，有助于进一步研究正常妊娠进展的分子机制。
