Division of Animal Sciences, University of Missouri, Columbia, MO 65211.
Division of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, MO 65211.
Proc Natl Acad Sci U S A. 2023 Dec 5;120(49):e2316410120. doi: 10.1073/pnas.2316410120. Epub 2023 Nov 29.
The uterus is vital for successful reproduction in mammals, and two different types of epithelia (luminal and glandular) are essential for embryo implantation and pregnancy establishment. However, the essential cellular and molecular factors and pathways governing postnatal epithelium maturation, determination, and differentiation in developing uterus are yet to be elucidated. Here, the epithelium of the neonatal mouse uterus was isolated and subjected to single-cell transcriptome (scRNA-seq) analysis. Both the undifferentiated epithelium and determined luminal epithelium were heterogeneous and contained several different cell clusters based on single-cell transcription profiles. Substantial gene expression differences were evident as the epithelium matured and differentiated between postnatal days 1 to 15. Two new glandular epithelium-expressed genes ( and ) were identified and validated by in situ hybridization. Trajectory analyses provided a framework for understanding epithelium maturation, lineage bifurcation, and differentiation. A candidate set of transcription factors and gene regulatory networks were identified that potentially direct epithelium lineage specification and morphogenesis. This atlas provides a foundation important to discover intrinsic cellular and molecular mechanisms directing uterine epithelium morphogenesis during a critical window of postnatal development.
子宫对于哺乳动物的成功繁殖至关重要，两种不同类型的上皮（腔上皮和腺上皮）对于胚胎着床和妊娠建立是必需的。然而，对于调控产后子宫上皮成熟、决定和分化的基本细胞和分子因素及途径仍有待阐明。在这里，我们分离了新生小鼠子宫的上皮，并进行了单细胞转录组（scRNA-seq）分析。未分化的上皮和已决定的腔上皮均具有异质性，并根据单细胞转录谱包含几个不同的细胞簇。随着上皮在产后第 1 天至 15 天之间的成熟和分化，明显存在大量基因表达差异。通过原位杂交鉴定并验证了两个新的腺上皮表达基因（和）。轨迹分析为理解上皮成熟、谱系分支和分化提供了一个框架。确定了一组候选转录因子和基因调控网络，它们可能指导上皮谱系特化和形态发生。这个图谱为发现指导产后发育关键窗口期子宫上皮形态发生的内在细胞和分子机制提供了重要基础。
