Innate molecular signature of stem cells from carious teeth influences differentiation toward endodermal endpoint

Nareshwaran Gnanasegaran , Vijayendran Govindasamy , Sabri Musa , Noor Hayaty Abu Kasim
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引用次数: 1

Abstract

The aim of this study was to characterize cells from carious teeth (DPSCs-CT) in terms of proliferation, mesoderm differentiation and gene expression profile as compared to DPSCs. Up-regulated genes in DPSCs-CT was detected via qPCR array and downstream trans-differentiation toward hepatocyte-like cells was performed. Additionally, qPCR array was employed to describe the genes pertaining to EMT and their possible mechanism. Despite basic characterizations favoured DPSCs, peculiarly DPSCs-CT had expressed a tremendous expression of hepatocyte growth factor gene (HGF; > 20 fold). To ascertain the notion that DPSCs-CT can be utilized for generating hepatic-like cells, we further de-toured the cells into hepatic lineage. As expected, DPSCs-CT expressed higher (>3 fold) hepatic markers such as SOX17, HNF3β, GATA4, AFP, TAT, TDO, AAT and ALB at both gene and protein levels. Improved homing capacity of DPSCs-CT and overall liver function were observed in bile duct ligation (BDL) treated rats. Mesenchymal-epithelial transition (MET) profiling was further conducted to elucidate the role HGF in promoting differentiation of DPSCs-CT and surprisingly, more than 40 genes related to MET were highly expressed in DPSCs-CT. To conclude, this information highlighted the potential of DPSCs-CT to differentiate into putative hepatocyte and subsequent usage for liver regeneration.

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龋齿干细胞的先天分子特征影响其向内胚层分化
本研究的目的是在龋齿细胞(DPSCs- ct)的增殖、中胚层分化和基因表达谱方面与DPSCs进行比较。通过qPCR阵列检测DPSCs-CT中上调基因,并进行向肝细胞样细胞的下游反分化。此外,利用qPCR阵列分析了EMT相关基因及其可能的机制。尽管基本特征有利于DPSCs,但DPSCs- ct特异表达了大量肝细胞生长因子基因(HGF;比;20倍)。为了确定DPSCs-CT可以用于产生肝样细胞的概念,我们进一步将细胞分解成肝脏谱系。正如预期的那样,DPSCs-CT在基因和蛋白水平上表达了更高(3倍)的肝脏标志物,如SOX17、HNF3β、GATA4、AFP、TAT、TDO、AAT和ALB。胆管结扎术后大鼠DPSCs-CT归巢能力及整体肝功能均有改善。为了进一步阐明HGF在促进DPSCs-CT分化中的作用,我们进行了间充质-上皮转化(MET)分析,令人惊讶的是,超过40个MET相关基因在DPSCs-CT中高表达。总之,这些信息强调了DPSCs-CT分化为假定的肝细胞和随后用于肝再生的潜力。
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