确定的条件控制大鼠原始胚胎外内胚层干细胞的形态二元论。

Stem cells and development Pub Date : 2023-12-01 Epub Date: 2023-11-10 DOI:10.1089/scd.2023.0187
Xiaoqiong Wang, Minjae Kim, Kyoung Hwa Jung, Young Gyu Chai, Bert Binas
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引用次数: 0

摘要

原始大鼠胚胎外内胚层(pXEN)干细胞系在体外无限期地保留早期胚胎外内胚的特征,但需要未知的血清因子,并表现出混合(间充质-上皮)表型。我们报道了两种化学定义的条件,其不同之处在于添加了细胞因子Lif和β-连环蛋白稳定药物Chir99021,并分别作为间充质和上皮形态类型实现了永久的自我更新。形态类型是相互转换和等势的,如形成分化良好的类器官所示。令人惊讶的是,两种形态类型的增殖都需要Lif型Gp130/Stat3信号传导(在没有添加Lif的情况下自分泌)和非经典Wnt信号传导(自分泌)。此外,上皮细胞的增殖和形态需要β-连环蛋白。有趣的是,间充质细胞也表达关键的上皮标志物,但这些标志物结构不正确和/或没有功能,表明处于启动状态。这些结果为研究胚胎外早期内胚层的增殖和可塑性提供了一个改进的平台,内胚层在体内以间充质和上皮形式出现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Defined Conditions Control the Morphological Dualism of Rat Primitive Extraembryonic Endoderm Stem Cells.

Rat primitive extraembryonic endoderm (pXEN) stem cell lines indefinitely preserve the characteristic features of the early extraembryonic endoderm (ExEn) in vitro, but require unknown serum factors and exhibit a hybrid (mesenchymal-epithelial) phenotype. We report two chemically defined conditions that differ by the addition of the cytokine leukemia inhibitory factor (Lif) and the β-catenin-stabilizing drug Chir99021, and enable permanent self-renewal as mesenchymal and epithelial morphotypes, respectively. The morphotypes are interconvertible and equipotent, as shown by the formation of well-differentiated organoids. Surprisingly, the proliferation of both morphotypes requires Lif-type Gp130/Stat3 signaling (autocrine in the absence of added Lif) and noncanonical Wnt signaling (autocrine). In addition, the epithelial version requires β-catenin for proliferation and morphology. Interestingly, the mesenchymal cells also express key epithelial markers, but those are improperly structured and/or not functional, indicating a primed state. These results provide an improved platform for studying the proliferation and plasticity of the early ExEn, which occurs in mesenchymal and epithelial forms in vivo.

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