Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Eur J Gastroenterol Hepatol. 2009 Oct;21(10):1191-8. doi: 10.1097/MEG.0b013e32832973fc.
Although telomerase activity has been analyzed in various normal and malignant tissues, including liver, it is still unknown to what extent telomerase can be associated with specific maturational lineage stages.
We assessed human telomerase activity, protein and gene expression for the telomerase reverse transcriptase, as well as expression of the telomeric template RNA hTER in hepatic stem cells and in various developmental stages of the liver from fetal to adult. In addition, the effect of growth factors on telomerase activity was analyzed in hepatic stem cells in vitro.
Telomerase was found to be highly active in fetal liver cells and was significantly higher than in hepatic stem cells, correlating with gene and protein expression levels. Activity in postnatal livers from all donor ages varied considerably and did not correlate with age or gene expression levels. The hter expression could be detected throughout the development. A short stimulation by growth factors of cultured hepatic stem cells did not increase telomerase activity.
Telomerase is considerably active in fetal liver and variably in postnatal livers. Although telomerase protein is present at varying levels in liver cells of all donor ages, gene expression is solely associated with fetal liver cells.
尽管端粒酶活性已在包括肝脏在内的各种正常和恶性组织中进行了分析,但仍不清楚端粒酶在何种程度上与特定的成熟谱系阶段相关。
我们评估了人类端粒酶活性、端粒酶逆转录酶的蛋白和基因表达,以及端粒模板 RNA hTER 在肝干细胞和从胎儿到成人的肝脏各个发育阶段的表达。此外,还分析了生长因子对肝干细胞中端粒酶活性的体外影响。
端粒酶在胎肝细胞中高度活跃,明显高于肝干细胞,与基因和蛋白表达水平相关。来自所有供体年龄的新生后肝脏的活性差异很大,与年龄或基因表达水平无关。hTER 的表达可在整个发育过程中检测到。培养的肝干细胞经短暂生长因子刺激后,端粒酶活性并未增加。
端粒酶在胎肝中高度活跃,在新生后肝脏中则活性不同。尽管端粒酶蛋白在所有供体年龄的肝细胞中存在不同水平,但基因表达仅与胎肝细胞相关。