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利用高密度寡核苷酸DNA芯片分析胎儿肝脏和出生后肝脏之间差异表达的基因。

Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array.

作者信息

Nagata Toshihito, Takahashi Yasuo, Ishii Yukimoto, Asai Satoshi, Sugahara Megumi, Nishida Yayoi, Murata Akiko, Chin Motoaki, Schichino Hiroyuki, Koshinaga Tsugumichi, Fukuzawa Masahiro, Mugishima Hideo

机构信息

Department of Advanced Medicine, Nihon University, School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.

出版信息

Int J Mol Med. 2003 Jun;11(6):713-21.

Abstract

The liver is an essential organ in humans not only for the production and storage of energy but also for detoxification of chemical compounds, but knowledge about changes in the gene expression profile in the human liver during the prenatal and postnatal periods is limited. Profiling of genes differentially expressed between the fetal liver (FL) and the postnatal liver (PNL) is one of the methods to investigate candidates affecting the difference in biological characteristics between FL and PNL. To identify genes differentially expressed between FL and PNL (childhood and adult liver), we analyzed the gene expression profiles across 9 FL and 14 PNL samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by k-nearest-neighbors (supervised learning method) and hierarchical clustering (unsupervised learning method) algorithms, we found 33 genes clearly discriminating between the FL group and PNL group. The functional classification of the 33 genes identified was related to several kinds of biological pathways, regulating the cell cycle (PCNA, CDC7L1, CCND3, YWHA1, PKMYT1), DNA replication and repair (RFC4, RECQ2, PCNA, NAP1L1), cell growth (IGF2, IGFBP2, PRSS11), hormonal signals (AR, SRD5A1, NR1I3), and cellular metabolism (E2-EPF, WWP1, CYP2C9, CYP2E1, CYP2A6, CYP2A7, CYP2A13, CYP4F2, CYP3A4, DDT). The results presented herein provide evidence of a differential expression profile of genes regulating the cell cycle, DNA replication and repair, cell growth, regulation of hormonal signals, and cellular metabolism, between FL and PNL in humans. The 33 genes identified in this study are suggested to be useful markers clearly discriminating between FL and PNL using the gene expression profile.

摘要

肝脏是人体中的一个重要器官,不仅负责能量的产生和储存,还参与化合物的解毒过程。然而,关于人类肝脏在产前和产后时期基因表达谱变化的知识却很有限。分析胎儿肝脏(FL)和产后肝脏(PNL)之间差异表达的基因是研究影响FL和PNL生物学特性差异的候选因素的方法之一。为了鉴定FL和PNL(儿童期和成人肝脏)之间差异表达的基因,我们使用高密度寡核苷酸DNA阵列分析了9个FL样本和14个PNL样本的基因表达谱。通过Mann-Whitney U检验,随后采用k近邻算法(监督学习方法)和层次聚类算法(无监督学习方法),我们发现了33个基因能够清晰地区分FL组和PNL组。所鉴定的这33个基因的功能分类与多种生物学途径相关,包括调节细胞周期(PCNA、CDC7L1、CCND3、YWHA1、PKMYT1)、DNA复制和修复(RFC4、RECQ2、PCNA、NAP1L1)、细胞生长(IGF2、IGFBP2、PRSS11)、激素信号(AR、SRD5A1、NR1I3)以及细胞代谢(E2-EPF、WWP1、CYP2C9、CYP2E1、CYP2A6、CYP2A7、CYP2A13、CYP4F2、CYP3A4、DDT)。本文呈现的结果提供了证据,表明人类FL和PNL在调节细胞周期、DNA复制和修复、细胞生长、激素信号调节以及细胞代谢的基因表达谱存在差异。本研究中鉴定出的这33个基因被认为是利用基因表达谱清晰区分FL和PNL 的有用标志物。

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