In a human menstrual cycle the endometrium undergoes remodeling, shedding and regeneration, all of which are driven by substantial gene expression changes in the underlying cellular hierarchy. Despite its importance in human fertility and regenerative biology, our understanding of this unique type of tissue homeostasis remains rudimentary. We characterized the transcriptomic transformation of human endometrium at single-cell resolution across the menstrual cycle, resolving cellular heterogeneity in multiple dimensions. We profiled the behavior of seven endometrial cell types, including a previously uncharacterized ciliated cell type, during four major phases of endometrial transformation, and found characteristic signatures for each cell type and phase. We discovered that the human window of implantation opens with an abrupt and discontinuous transcriptomic activation in the epithelia, accompanied with a widespread decidualization feature in the stromal fibroblasts. Our study provides a high-resolution molecular and cellular characterization of human endometrial transformation across the menstrual cycle, providing insights into this essential physiological process.

在人类的月经周期中，子宫内膜会发生重塑，脱落和再生，所有这些都由潜在的细胞层次中大量的基因表达变化驱动。尽管它在人类生育力和再生生物学中很重要，但我们对这种组织稳态的独特类型的理解仍然是基本的。我们在整个月经周期的单细胞分辨率下表征了人类子宫内膜的转录组转化，从而在多个维度上解决了细胞异质性。我们在子宫内膜转化的四个主要阶段分析了七种子宫内膜细胞类型（包括以前未鉴定的纤毛细胞类型）的行为，并发现了每种细胞类型和阶段的特征性特征。我们发现人类的植入窗口打开与上皮细胞的突然和不连续的转录组激活，并伴随在基质成纤维细胞中广泛的蜕膜化特征。我们的研究提供了跨月经周期的人类子宫内膜转化的高分辨率分子和细胞表征，为这一基本的生理过程提供了见识。