Mouse embryonic stem cells lacking p38α and p38δ can differentiate to endothelial cells, smooth muscle cells, and epithelial cells
Mouse embryonic stem cells lacking p38α and p38δ can differentiate to endothelial cells, smooth muscle cells, and epithelial cells
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DOI：
10.1016/j.diff.2009.05.006
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发表时间：
2009-09-01
期刊：
影响因子：
2.9
通讯作者：
Guo, Yan-Lin
中科院分区：
文献类型：
--
作者：
Chakraborty, Samujjwal;Kang, Baobin;Guo, Yan-Lin
p38 丝裂原激活蛋白 (MAP) 激酶 (p38) 是调节各种细胞过程的重要信号分子。已在哺乳动物细胞中鉴定出 p38 家族的四种亚型：p38 α、p38 β、p38 γ 和 p38 δ。先前的研究表明，p38 α 敲除对小鼠胚胎具有致命性。在细胞水平上，p38a 在小鼠胚胎干细胞 (ESC) 中大量表达，但 p38 α 敲除 (p38 α-/-) ESC 可以分化为内皮细胞 (EC)、平滑肌细胞 (SMC) 和神经元。我们推测，p38 α-/- ESC 中 p38 α 功能的缺失可能会被其他亚型的冗余功能所补偿。为了验证这一假设，我们使用 siRNA 方法来敲低 ESC 中第二丰富的异构体 p38 delta 的表达。从 p38 α-/- ESC 建立稳定表达 p38 delta siRNA 的 ESC，导致 p38 delta mRNA 表达减少 80%。然而，这些缺乏 p38 α 和 p38 δ 的 ESC 仍然可以分化为 EC 和 SMC。我们扩展了我们的研究范围，以测试这些细胞是否可以分化为上皮细胞，其中 p38 δ 已被证明可以调节表皮分化。我们的结果再次证明ESC分化为上皮细胞不依赖于p38α和p38δ。我们得出的结论是，p38α和p38δ对于ESC分化为EC、SMC或上皮细胞并不是必需的，尽管大量研究表明这两种激酶调节上述细胞中的各种细胞活动。我们的结果强调了 p38 MAP 激酶在 ESC 分化中发挥的作用可能不如在完全分化的体细胞的细胞活动调节中发挥的作用重要的可能性。 (C) 2009 年国际分化学会。由爱思唯尔有限公司出版。保留所有权利。
The p38 mitogen-activated protein (MAP) kinases (p38) are important signaling molecules that regulate various cellular processes. Four isoforms of p38 family, p38 alpha, p38 beta, p38 gamma, and p38 delta, have been identified in mammalian cells. Previous studies have shown that p38 alpha knockout is embryonic lethal in mice. At the cellular level, p38a is abundantly expressed in mouse embryonic stem cells (ESCs), but p38 alpha knockout (p38 alpha-/-) ESCs can differentiate to endothelial cells (ECs), smooth muscle cells (SMCs), and neurons. We speculate that the lost function of p38 alpha in p38 alpha-/- ESCs may be compensated for by the redundant function of other isoforms. To test this hypothesis, we used siRNA approach to knockdown the expression of p38 delta, the second abundant isoform in ESCs. ESCs stably expressing p38 delta siRNA were established from p38 alpha-/- ESCs, resulting in 80% reduction of p38 delta mRNA expression. However, these ESCs, deficient of both p38 alpha and p38 delta, could still differentiate into ECs and SMCs. We extended our investigation to test if these cells can differentiate into epithelial cells in which p38 delta has been shown to regulate epidermis differentiation. Our results demonstrate again that ESC differentiation to epithelial cells is independent of p38 alpha and p38 delta. We conclude that p38 alpha and p38 delta are not essential for ESC differentiating into ECs, SMCs, or epithelial cells although numerous studies have shown that the two kinases regulate various cellular activities in aforementioned cells. Our results highlight the possibility that p38 MAP kinases may play less significant roles in ESC differentiation than in the regulation of cellular activities of fully differentiated somatic cells. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.