Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.
Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.
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DOI：
10.1371/journal.pone.0007166
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发表时间：
2009-09-24
期刊：
影响因子：
3.7
通讯作者：
Kang SK
中科院分区：
文献类型：
--
作者：
Kim JH;Jee MK;Lee SY;Han TH;Kim BS;Kang KS;Kang SK
为了阐明POU结构域转录因子Oct 4在脂肪组织基质细胞（ATSCs）中的作用，我们研究了Oct 4表达和其他胚胎基因在完全分化细胞中的调控，以及在基因和蛋白水平上的表达。ATSCs和一些未成熟细胞在分化成特定谱系之前和之后常规地表达Oct 4蛋白。在这里，我们证明了Oct 4在ATSCs中对细胞增殖和分化的作用。外源性Oct 4通过对干性基因（如Oct 4、Nanog、Sox 2和Rex 1）的表观遗传重编程来改善成体ATSCs细胞增殖和分化能力。Oct 4直接或间接诱导ATSCs重编程沿着JAK/STAT 3和ERK 1/2的激活。外源性Oct 4在神经谱系中比在中胚层谱系中优先引入转分化。全局基因表达分析结果表明，Oct 4调节的靶基因可以被表征为差异调节的基因，如多能性标志物NANOG、SOX 2和KLF 4以及未分化干细胞标志物FOXD 1、CDC 2和EPHB 1。负调控的基因包括FAS、TNFR、COL 6A 1、JAM 2、FOXQ 1、FOXO 1、NESTIN、SMAD 3、SLIT 3、DKK 1、WNT 5A、BMP 1和GLIS 3，这些基因与分化过程以及许多新基因有关。最后，我们已经证明了Oct 4/ATSCs的治疗效用被引入到小鼠创伤性脑中，移植的细胞比对照ATSCs更有效地诱导具有高治疗模式的再生活性。移植的Oct 4/ATSCs有效迁移并转分化为海马中携带动作电位的功能性神经元，并促进损伤腔的改善。
To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages. Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities.
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