Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109.
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2404775121. doi: 10.1073/pnas.2404775121. Epub 2024 Oct 29.
The human uterus is a complex and dynamic organ whose lining grows, remodels, and regenerates every menstrual cycle or upon tissue damage. Here, we applied single-cell RNA sequencing to profile more the 50,000 uterine cells from both the endometrium and myometrium of five healthy premenopausal individuals, and jointly analyzed the data with a previously published dataset from 15 subjects. The resulting normal uterus cell atlas contains more than 167K cells, representing the lymphatic endothelium, blood endothelium, stromal, ciliated epithelium, unciliated epithelium, and immune cell populations. Focused analyses within each major cell type and comparisons with subtype labels from prior studies allowed us to document supporting evidence, resolve naming conflicts, and propose a consensus annotation system of 39 subtypes. We release their gene expression centroids, differentially expressed genes, and messenger Ribonucleic Acid (mRNA) patterns of literature-based markers as a shared community resource. We identify multiple potential progenitor cells: compartment-wide progenitors for each major cell type and potential cross-lineage multipotent stromal progenitors that may replenish the epithelial, stromal, and endothelial compartments. Furthermore, many cell types and subtypes exhibit shifts in cell number and transcriptomes across different phases of the menstrual cycle. Finally, comparisons between premenopausal, postpartum, and postmenopausal samples revealed substantial alterations in tissue composition, particularly in the proportions of stromal, endothelial, and immune cells. The cell taxonomy and molecular markers we report here are expected to inform studies of both basic biology of uterine function and its disorders.
人类子宫是一个复杂而动态的器官,其内膜在每个月经周期或组织损伤时都会生长、重塑和再生。在这里,我们应用单细胞 RNA 测序技术对来自五名健康绝经前个体的子宫内膜和子宫肌层的超过 50000 个子宫细胞进行了分析,并与之前发表的来自 15 个个体的数据集进行了联合分析。由此产生的正常子宫细胞图谱包含超过 167000 个细胞,代表了淋巴内皮细胞、血液内皮细胞、基质细胞、纤毛上皮细胞、非纤毛上皮细胞和免疫细胞群体。在每个主要细胞类型内进行的重点分析以及与先前研究中的亚型标签的比较,使我们能够提供支持证据、解决命名冲突,并提出 39 个亚型的共识注释系统。我们发布了它们的基因表达质心、差异表达基因和文献标记物的信使核糖核酸 (mRNA) 模式,作为一个共享的社区资源。我们确定了多个潜在的祖细胞:每个主要细胞类型的全室祖细胞和潜在的跨谱系多能基质祖细胞,它们可能补充上皮、基质和内皮室。此外,许多细胞类型和亚型在月经周期的不同阶段表现出细胞数量和转录组的变化。最后,绝经前、产后和绝经后样本之间的比较显示出组织组成的实质性改变,特别是基质、内皮和免疫细胞的比例。我们在这里报告的细胞分类和分子标记物有望为子宫功能及其障碍的基础生物学研究提供信息。