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Tcea3 Regulates the Vascular Differentiation Potential of Mouse Embryonic Stem Cells

2013; Volume: 16; Issue: 1 Linguagem: Inglês

10.3727/105221613x13776146743343

1555-3884

Young Cha, Sun‐Hee Heo, Hee-Jin Ahn, Bosco Seong Kyu Yang, Jihwan Song, Wonhee Suh, Kyung‐Soon Park,

Developmental Biology and Gene Regulation

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.