Lefty1 and Lefty2 Control the Balance Between Self-Renewal and Pluripotent Differentiation of Mouse Embryonic Stem Cells
Lefty1 and Lefty2 Control the Balance Between Self-Renewal and Pluripotent Differentiation of Mouse Embryonic Stem Cells
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DOI：
10.1089/scd.2013.0220
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
Park, Kyung-Soon
中科院分区：
文献类型：
--
作者：
Kim, Dae-Kwan;Cha, Young;Park, Kyung-Soon
Lefty表达已被认为是干细胞标记，因为Lefty在未分化的胚胎干细胞（ESC）和胚泡中富集。本研究旨在探讨Lefty1和Lefty2在维持小鼠胚胎干细胞（mESCs）自我更新和多能性中的作用。在非分化条件下，抑制Lefty1或Lefty2的表达不会改变mESCs的自我更新特性，但这些基因的抑制确实会影响Smad2的磷酸化和分化。Lefty1敲除mESCs显示Smad2的磷酸化增强，分化潜能增加，而Lefty2敲除mESCs显示Smad2的磷酸化降低，在分化信号存在下自我更新增强。在体内，从Lefty2基因敲除的胚胎干细胞发育而来的畸胎瘤含有大量未成熟神经上皮细胞的扩张，这是恶性畸胎瘤的标志。综上所述，这些结果表明，Lefty1和Lefty2的最佳表达对于mESCs平衡分化为三个胚层至关重要。
Lefty expression has been recognized as a stemness marker because Lefty is enriched both in undifferentiated embryonic stem cells (ESCs) and in blastocysts. Here, we examined the function ofLefty1andLefty2in the maintenance of self-renewal and pluripotency of mouse ESCs (mESCs). Suppression ofLefty1orLefty2expression in mESCs did not alter the self-renewal properties of mESCs under nondifferentiating conditions, but suppression of these genes did affect Smad2 phosphorylation and differentiation.Lefty1knockdown mESCs showed enhanced phosphorylation of Smad2 and increased differentiation potential, whereasLefty2knockdown mESCs exhibited reduced phosphorylation of Smad2 and enhanced self-renewal in the presence of a differentiation signal. In vivo, teratomas developed fromLefty2knockdown mESCs contained massive expansions of immature neuroepithelium, a marker of malignant teratomas. Taken together, these results suggest that optimal expression ofLefty1andLefty2is critical for the balanced differentiation of mESCs into three germ layers.