Clonal Isolation of an Intermediate Pluripotent Stem Cell State
Clonal Isolation of an Intermediate Pluripotent Stem Cell State
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DOI：
10.1002/stem.1330
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发表时间：
2013-05-01
期刊：
影响因子：
5.2
通讯作者：
Li, Meng
中科院分区：
文献类型：
--
作者：
Chang, Kuo-Hsuan;Li, Meng
不同胚胎来源的多能干细胞响应不同的信号传导途径。胚胎干细胞（ESC）来源于植入前胚胎的内细胞团，依赖于LIF-Stat 3信号传导，而从植入后胚胎建立的外胚层干细胞（EpiSC）需要激活素-Smad 2/3信号传导。最近的研究揭示了ESC的异质性和中间多能干细胞群体的存在，其对生长因子的反应性，基因表达模式和相关的染色质特征与ESC和EpiSC之间的状态相容。然而，它仍然是未知的，这些细胞群是否代表一个稳定的实体在单细胞水平。在这里，我们描述了从小鼠胚胎干细胞的克隆干细胞的鉴定与全球基因表达谱代表这样一个国家。这些多能干细胞在单细胞水平上对LIF-Stat 3和激活素-Smad 2/3表现出双重反应性，因此被称为中间外胚层干细胞（IESC）。此外，这些细胞在体外胚状体分化过程中显示出加速的时间基因表达动力学，这与比ESC更高级的分化阶段一致。IESC的成功分离支持这样的概念，即从幼稚基态到谱系承诺的跨越逐渐发生，其中过渡里程碑可以被捕获为克隆形成实体。我们的发现提供了一个新的模型，以更好地理解多个多能状态。干细胞2013;31：918-927
Pluripotent stem cells of different embryonic origin respond to distinct signaling pathways. Embryonic stem cells (ESCs), which are derived from the inner cell mass of preimplantation embryos, are dependent on LIF-Stat3 signaling, while epiblast stem cells (EpiSCs), which are established from postimplantation embryos, require activin-Smad2/3 signaling. Recent studies have revealed heterogeneity of ESCs and the presence of intermediate pluripotent stem cell populations, whose responsiveness to growth factors, gene expression patterns, and associated chromatic signatures are compatible to a state in between ESCs and EpiSCs. However, it remains unknown whether such cell populations represent a stable entity at single-cell level. Here, we describe the identification of clonal stem cells from mouse ESCs with global gene expression profiles representing such a state. These pluripotent stem cells display dual responsiveness to LIF-Stat3 and activin-Smad2/3 at single-cell level and thus named as intermediate epiblast stem cells (IESCs). Furthermore, these cells show accelerated temporal gene expression kinetics during embryoid body differentiation in vitro consistent with a more advanced differentiation stage than that of ESCs. The successful isolation of IESCs supports the notion that traverse from naive ground state toward lineage commitment occurs gradually in which transition milestones can be captured as clonogenic entity. Our finding provides a new model to better understand the multiple pluripotent states. STEM CELLS 2013;31:918-927