卵圆肝干细胞模型中大鼠肝脏再生的转录组分析

Transcriptome analysis of rat liver regeneration in a model of oval hepatic stem cells.

作者信息

Cimica Velasco, Batusic Danko, Chen Yonglong, Hollemann Thomas, Pieler Tomas, Ramadori Giuliano

机构信息

Department of Gastroenterology and Endocrinology, Georg-August-University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany.

出版信息

Genomics. 2005 Sep;86(3):352-64. doi: 10.1016/j.ygeno.2005.05.001.

DOI:10.1016/j.ygeno.2005.05.001

PMID:15993033

Abstract

We have performed serial analysis of gene expression of the regenerating liver. In the rat model of partial hepatectomy and 2-acetamidofluorene treatment liver regeneration recruits hepatic stem cells referred to as oval cells. We analyzed a total of 153,057 tags in livers from normal control (52,343 tags), from sham 2-acetamidofluorene-treated control (50,502 tags), and from the early stage of oval cell proliferation (50,212 tags). Comparative analysis of the three transcriptomes identified 27 up-regulated and 18 down-regulated genes. Real-time PCR analysis confirmed 11 temporally regulated genes that correlate with oval cell development. Interestingly, we found by Western blot protein analysis of regenerating livers that the cell cycle gene Cdc42 was induced concomitant with the proliferation marker cyclin D1 and the oval cell marker alpha-fetoprotein. Our studies provide new insights into the molecular mechanism of liver regeneration through oval cells.

摘要

我们对再生肝脏进行了基因表达的系列分析。在部分肝切除和2-乙酰氨基芴处理的大鼠肝脏再生模型中，肝脏再生会募集被称为卵圆细胞的肝干细胞。我们分析了来自正常对照肝脏（52,343个标签）、假2-乙酰氨基芴处理对照肝脏（50,502个标签）以及卵圆细胞增殖早期肝脏（50,212个标签）的总共153,057个标签。对这三个转录组的比较分析确定了27个上调基因和18个下调基因。实时PCR分析证实了11个与卵圆细胞发育相关的时间调控基因。有趣的是，我们通过对再生肝脏的蛋白质印迹分析发现，细胞周期基因Cdc42与增殖标志物细胞周期蛋白D1和卵圆细胞标志物甲胎蛋白同时被诱导。我们的研究为通过卵圆细胞进行肝脏再生的分子机制提供了新的见解。