Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Sci Rep. 2019 Mar 14;9(1):4557. doi: 10.1038/s41598-019-40923-w.
The uterus is a remarkable organ that must guard against infections while maintaining the ability to support growth of a fetus without rejection. The Hoxa10 and Hoxa11 genes have previously been shown to play essential roles in uterus development and function. In this report we show that the Hoxa9,10,11, Hoxc9,10,11, Hoxd9,10,11 genes play a redundant role in the formation of uterine glands. In addition, we use single cell RNA-seq to create a high resolution gene expression atlas of the developing wild type mouse uterus. Cell types and subtypes are defined, for example dividing endothelial cells into arterial, venous, capillary, and lymphatic, while epithelial cells separate into luminal and glandular subtypes. Further, a surprising heterogeneity of stromal and myocyte cell types are identified. Transcription factor codes and ligand/receptor interactions are characterized. We also used single cell RNA-seq to globally define the altered gene expression patterns in all developing uterus cell types for two Hox mutants, with 8 or 9 mutant Hox genes. The mutants show a striking disruption of Wnt signaling as well as the Cxcl12/Cxcr4 ligand/receptor axis.
子宫是一个非凡的器官，它必须防止感染，同时保持支持胎儿生长而不被排斥的能力。HOXA10 和 HOXA11 基因先前已被证明在子宫发育和功能中发挥重要作用。在本报告中，我们表明 HOXA9、10、11、HOXC9、10、11、HOXD9、10、11 基因在子宫腺形成中具有冗余作用。此外，我们使用单细胞 RNA-seq 为发育中的野生型小鼠子宫创建了高分辨率的基因表达图谱。定义了细胞类型和亚型，例如将内皮细胞分为动脉、静脉、毛细血管和淋巴管，而将上皮细胞分为腔和腺型。此外，还鉴定了基质和肌细胞类型的惊人异质性。转录因子代码和配体/受体相互作用也得到了描述。我们还使用单细胞 RNA-seq 全局定义了两种 Hox 突变体（8 或 9 个突变 Hox 基因）中所有发育中的子宫细胞类型的改变的基因表达模式。突变体显示出 Wnt 信号以及 CXCL12/CXCR4 配体/受体轴的惊人破坏。
