Transcriptional ontogeny of the developing liver.

Transcriptional ontogeny of the developing liver.
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DOI:
10.1186/1471-2164-13-33
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发表时间:
2012-01-19
期刊:
影响因子:
4.4
通讯作者:
Corton JC
Corton JC
中科院分区:
生物学2区
文献类型:
--
作者:
Lee JS;Ward WO;Knapp G;Ren H;Vallanat B;Abbott B;Ho K;Karp SJ;Corton JC

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在胚胎发生过程中,肝脏来源于位于消化道内壁的内胚层细胞。这些内胚层祖细胞有助于形成许多器官的实质,包括肝脏和胰腺。在器官发生的早期,胎儿肝脏由造血干细胞组成,造血干细胞是许多血细胞(包括有核红细胞)的来源。对肝脏从发育早期到成年期发生的转录变化进行了全面分析。我们使用全基因组微阵列,与成年小鼠肝脏(PND 67)相比,在妊娠(GD)11.5、12.5、13.5、14.5、16.5和19天以及新生儿(出生后(PND)7和32天)发育小鼠肝脏中的基因表达变化。与成人相比,胎儿肝脏和新生儿肝脏在较小程度上表现出显著的基因表达差异。胎肝特征的典型途径分析表明,细胞复制和DNA保真度的重要功能增加,而中间代谢的大多数代谢途径表达不足。将该数据集与许多先前发表的微阵列数据集进行比较,揭示了1)小鼠和人类的胎儿肝脏与胰腺之间的惊人相似性,2)胎儿中的有核红细胞签名,以及3)在整个发育过程中大多数异生物质代谢基因的表达不足,除了与肝细胞中的造血细胞或细胞增殖相关的许多转运蛋白。总的来说,这些发现揭示了肝脏发育和成熟过程中基因表达变化的复杂性,并为预测早期生命阶段对化学和药物暴露的反应提供了基础。
During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver was carried out. We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND) 7 and 32) compared to that in the adult liver (PND67) using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes. Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.
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发表时间: 2002-06-01
影响因子: 6
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DOI: 10.1080/00498250600861751
发表时间: 2006-10-01
期刊: XENOBIOTICA
影响因子: 1.8
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