Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification.

Atsushi Suzuki, Angel Raya, Yasuhiko Kawakami, Masanobu Morita, Takaaki Matsui, Kinichi Nakashima, Fred H Gage, Concepción Rodríguez-Esteban, Juan Carlos Izpisúa Belmonte
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引用次数: 75

Abstract

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.

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通过纳米介导的中胚层分化逆转维持胚胎干细胞多能性。
胚胎干细胞(ESCs)可以在培养中无限繁殖,同时保留向生物体中任何细胞类型分化的能力。然而,ESC多能性的分子和细胞机制尚不清楚。我们描述了一个由小鼠ESCs通过骨形态发生蛋白刺激产生的早期中胚层特异性(EM)祖细胞群体。我们进一步表明,多能性ESCs是由EM祖细胞通过含有分化同源结构域的蛋白Nanog的作用而再生的,而Nanog在EM祖细胞中又通过白血病抑制因子和早期中胚层转录因子T/Brachyury的联合作用而上调。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。
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