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Porcine Skin-Derived Progenitor (SKP) Spheres and Neurospheres: Distinct Stemness Identified by Microarray Analysis

机译:猪皮肤衍生祖细胞(SKP)球和神经球:通过微阵列分析鉴定出的不同干性

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摘要

Skin-derived progenitors (SKP) are neural crest derived and can generate neural and mesodermal progeny in vitro, corresponding to the multipotency of neural crest stem cells. Likewise, neural stem/progenitor cells (displaying as neurospheres) have the capacity of self-renewing, and can produce most phenotypes in the nervous system. Both form spheres when cultured with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Although the “stemness” of neural stem/progenitor cells has been extensively investigated, the molecular comparison of SKP spheres and neurospheres has not been elucidated. Here, SKP spheres and neurospheres from the same individual porcine fetuses were isolated with the same culture medium, and the multipotency was tested by in vitro differentiation assays. Microarray analysis was used to illustrate the “stemness” of SKP spheres and neurospheres. The upregulated genes that were in common in the SKP spheres and neurospheres are involved in ribosome, tight junction, gap junction, cell communication, calcium signaling, ErbB signaling, JAK–STAT signaling, MAPK signaling, etc. The differentially expressed genes between SKP spheres and neurospheres are mainly involved in ECM–receptor interaction and the transforming growth factor-beta (TGF-β) signaling pathway. Finally, treatment with leukemia inhibitory factor (LIF) or MEK inhibitor results in a distinctive impact on the “stemness” and differentiation genes of SKP spheres and neurospheres. Thus, the cell-intrinsic genetic program may contribute to the innate “stemness” of SKP spheres and neurospheres in a similar local microenvironment.
机译:皮肤来源的祖细胞(SKP)是神经c衍生的,可以在体外产生神经和中胚层的后代,与神经c干细胞的多能性相对应。同样,神经干/祖细胞(显示为神经球)具有自我更新的能力,并且可以在神经系统中产生大多数表型。与表皮生长因子(EGF)和碱性成纤维细胞生长因子(bFGF)培养时,两者均形成球体。尽管已经对神经干/祖细胞的“干性”进行了广泛的研究,但尚未阐明SKP球和神经球的分子比较。在这里,使用相同的培养基分离出来自同一只猪胎儿的SKP球和神经球,并通过体外分化试验测试了多能性。微阵列分析用于说明SKP球和神经球的“干性”。 SKP球和神经球中常见的上调基因涉及核糖体,紧密连接,间隙连接,细胞通讯,钙信号传导,ErbB信号传导,JAK–STAT信号传导,MAPK信号传导等。SKP球之间的差异表达基因神经球主要参与ECM-受体相互作用和转化生长因子-β(TGF-β)信号通路。最后,用白血病抑制因子(LIF)或MEK抑制剂治疗会对SKP球和神经球的“干性”和分化基因产生显着影响。因此,在相似的局部微环境中,细胞内在遗传程序可能有助于SKP球和神经球的先天“干”。

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