Single cell RNA-seq study of wild type and Hox mutant developing uterus. Single cell RNA-seq study of wild type and Hox mutant developing uterus

This study identifies a novel role for the Hoxc9,10,11 genes in uterine gland formation. This function is redundant with the Hoxa9,10,11 and Hoxd9,10,11 genes and is only seen in a sensitized genotype with reduced expression of these paralogs. We further used scRNA-seq to define the gene expression patterns of the multiple cell types of the developing uterus. The results define the gene expression patterns driving lineage specific development. In addition scRNA-seq was used to characterize the perturbed gene expression levels of all developing uterus cell types in the ACD+/- and ACD+/-WTA11 mutants. Particularly striking was the reduced Wnt signaling and the disruption of the Cxcl12/Cxcr4 axis in the mutants. Overall design: Using droplet RNA sequencing, transcriptomes of single cells from wild-type and Hox mutant mouse uteri were analyzed

本研究揭示了Hoxc9、10、11基因在子宫腺体形成中的全新功能。该功能与Hoxa9、10、11及Hoxd9、10、11基因存在功能冗余，且仅在这些旁系同源基因表达水平降低的致敏基因型中方可观测到。我们进一步通过单细胞RNA测序（single-cell RNA sequencing，scRNA-seq）明确了发育中子宫多种细胞类型的基因表达模式，该结果阐明了驱动谱系特异性发育的基因表达调控规律。此外，本研究还利用scRNA-seq对ACD+/-与ACD+/-WTA11突变体中所有发育中子宫细胞类型的扰动基因表达水平进行了表征。尤为引人注目的是，突变体中Wnt信号通路活性显著降低，且Cxcl12/Cxcr4信号轴遭到破坏。总体实验设计：采用液滴RNA测序技术，对野生型及Hox突变小鼠子宫的单细胞转录组进行分析。