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Tcea3 regulates the vascular differentiation potential of mouse embryonic stem cells

机译:Tcea3调节小鼠胚胎干细胞的血管分化潜能

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Tcea3 is present in high concentrations in mouse embryonic stem cells (mESCs) and functions to activate Lefty1, a negative regulator of Nodal signaling. The Nodal pathway has numerous biological activities, including mesoderm induction and patterning in early embryogenesis. Here, we demonstrate that the suppression of Tcea3 in mESCs shifts the cells from pluripotency into enhanced mesoderm development. Vascular endothelial growth factor A (VEGFA) and VEGFC, major transcription factors that regulate vasculogenesis, are activated in Tcea3 knocked down (Tcea3 KD) mESCs. Moreover, differentiating Tcea3 KD mESCs have perturbed gene expression profiles with suppressed ectoderm and activated mesoderm lineage markers. Most early differentiating Tcea3 KD cells expressed Brachyury-T, a mesoderm marker, whereas control cells did not express the gene. Finally, development of chimeric embryos that included Tcea3 KD mESCs was perturbed.
机译:Tcea3高浓度存在于小鼠胚胎干细胞(mESCs)中,并起着激活Lefty1(Nodal信号的负调节剂)的作用。 Nodal途径具有多种生物学活性,包括中胚层诱导和早期胚胎发生中的模式。在这里,我们证明了mESCs中Tcea3的抑制将细胞从多能性转移到增强的中胚层发育中。血管内皮生长因子A(VEGFA)和VEGFC,调节血管生成的主要转录因子,在敲除的Tcea3(Tcea3 KD)mESC中被激活。此外,差异化的Tcea3 KD mESCs具有受抑制的外胚层和活化的中胚层谱系标记的基因表达谱。大多数早期分化的Tcea3 KD细胞表达中胚层标记Brachyury-T,而对照细胞不表达该基因。最后,包括Tcea3 KD mESCs的嵌合胚胎的发育受到干扰。

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