Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
FASEB J. 2024 May 15;38(9):e23632. doi: 10.1096/fj.202400303R.
The upper Müllerian duct (MD) is patterned and specified into two morphologically and functionally distinct organs, the oviduct and uterus. It is known that this regionalization process is instructed by inductive signals from the adjacent mesenchyme. However, the interaction landscape between epithelium and mesenchyme during upper MD development remains largely unknown. Here, we performed single-cell transcriptomic profiling of mouse neonatal oviducts and uteri at the initiation of MD epithelial differentiation (postnatal day 3). We identified major cell types including epithelium, mesenchyme, pericytes, mesothelium, endothelium, and immune cells in both organs with established markers. Moreover, we uncovered region-specific epithelial and mesenchymal subpopulations and then deduced region-specific ligand-receptor pairs mediating mesenchymal-epithelial interactions along the craniocaudal axis. Unexpectedly, we discovered a mesenchymal subpopulation marked by neurofilaments with specific localizations at the mesometrial pole of both the neonatal oviduct and uterus. Lastly, we analyzed and revealed organ-specific signature genes of pericytes and mesothelial cells. Taken together, our study enriches our knowledge of upper MD development, and provides a manageable list of potential genes, pathways, and region-specific cell subtypes for future functional studies.
上部 Müllerian 管(MD)被构造成两种形态和功能上不同的器官,即输卵管和子宫。已知这个区域化过程是由相邻间充质的诱导信号指导的。然而,在上部 MD 发育过程中上皮和间充质之间的相互作用景观在很大程度上仍然未知。在这里,我们对新生小鼠输卵管和子宫在 MD 上皮分化开始时(出生后第 3 天)进行了单细胞转录组分析。我们使用已建立的标记物鉴定了两个器官中的主要细胞类型,包括上皮、间充质、周细胞、间皮、内皮和免疫细胞。此外,我们发现了具有区域特异性的上皮和间充质亚群,然后推断出沿头尾轴介导间充质-上皮相互作用的区域特异性配体-受体对。出乎意料的是,我们发现了一个标记有神经丝的间充质亚群,该亚群在新生输卵管和子宫的系膜极具有特定的定位。最后,我们分析并揭示了周细胞和间皮细胞的器官特异性特征基因。总之,我们的研究丰富了我们对上部 MD 发育的认识,并为未来的功能研究提供了一个潜在基因、途径和区域特异性细胞亚型的可管理列表。