Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification
Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification
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DOI：
10.1038/ncpcardio0442
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发表时间：
2006-03
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影响因子：
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通讯作者：
A. Suzuki;Á. Raya;Y. Kawakami;Masanobu Morita;Takaaki Matsui;K. Nakashima;F. Gage;Concepción Rodríguez-Esteban;J. Belmonte
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文献类型：
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作者：
A. Suzuki;Á. Raya;Y. Kawakami;Masanobu Morita;Takaaki Matsui;K. Nakashima;F. Gage;Concepción Rodríguez-Esteban;J. Belmonte
胚胎干细胞（ESC）可以在培养中无限繁殖，同时保留分化成生物体中任何细胞类型的能力。然而，ESC多能性的分子和细胞机制知之甚少。我们的特点是人口的早期中胚层指定（EM）的祖细胞，是从小鼠胚胎干细胞的骨形态发生蛋白刺激。我们进一步表明，多能性ESC是积极再生EM祖细胞的行动的分歧同源结构域含有蛋白Nanog，这反过来又是上调EM祖细胞的白血病抑制因子和早期中胚层转录因子T/Brachyury的联合作用。这些发现揭示了白血病抑制因子Nanog和骨形态发生蛋白在ESC自我更新中的特定作用，并为ESC多能性的细胞基础提供了新的见解。
Embryonic stem cells (ESCs) can be propagated indefinitely in culture, while retaining the ability to differentiate into any cell type in the organism. The molecular and cellular mechanisms underlying ESC pluripotency are, however, poorly understood. We characterize a population of early mesoderm-specified (EM) progenitors that is generated from mouse ESCs by bone morphogenetic protein stimulation. We further show that pluripotent ESCs are actively regenerated from EM progenitors by the action of the divergent homeodomain-containing protein Nanog, which, in turn, is upregulated in EM progenitors by the combined action of leukemia inhibitory factor and the early mesoderm transcription factor T/Brachyury. These findings uncover specific roles of leukemia inhibitory factor, Nanog, and bone morphogenetic protein in the self-renewal of ESCs and provide novel insights into the cellular bases of ESC pluripotency.