Dyrk1a dosage effects on the transcriptome of embryonic hearts from the Dp1Tyb mouse model of Down syndrome using bulk RNAseq

We performed bulk RNAseq on whole hearts from E13.5 Dp1Tyb embryos and from wild-type littermates, as well as hearts from E13.5 Dp1TybDyrk1a+/+/- embryos and wild-type littermates. Analysis showed the expected increased expression of the Hsa21-orthologous genes on Mmu16 that are present in 3 copies. Gene set enrichment analysis identified pathways that are altered in Dp1Tyb hearts. Some of these changes were dependent on 3 copies of Dyrk1a. RNAseq on 5 E13.5 Dp1Tyb embryonic hearts and 5 wild-type littermate embryonic hearts, and on 5 E13.5 Dp1TybDyrk1a+/+/- embryonic hearts and 5 wild-type littermate embryonic hearts.本研究针对胚胎发育第13.5天（E13.5）的Dp1Tyb胚胎、野生型同窝仔鼠的完整心脏，以及同胎龄Dp1TybDyrk1a+/+/-胚胎的完整心脏与野生型同窝仔鼠的完整心脏开展了批量RNA测序（bulk RNAseq）。分析结果显示，位于小鼠16号染色体（Mmu16）上、拷贝数为3的人类21号染色体（Hsa21）同源基因的表达量出现了预期的上调。通过基因集富集分析，本研究识别出Dp1Tyb小鼠心脏中发生表达紊乱的信号通路，其中部分调控异常依赖于Dyrk1a基因的三拷贝剂量。本次测序共纳入5例E13.5 Dp1Tyb胚胎心脏、5例野生型同窝胚胎心脏，以及5例E13.5 Dp1TybDyrk1a+/+/-胚胎心脏与5例野生型同窝胚胎心脏。