Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.

Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.
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DOI:
10.1038/msb.2009.37
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发表时间:
2009
影响因子:
9.9
通讯作者:
Kislinger, Thomas
Kislinger, Thomas
中科院分区:
生物学1区
文献类型:
--
作者:
Cox, Brian;Kotlyar, Max;Evangelou, Andreas I.;Ignatchenko, Vladimir;Ignatchenko, Alex;Whiteley, Kathie;Jurisica, Igor;Adamson, S. Lee;Rossant, Janet;Kislinger, Thomas

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胎盘异常与人类妊娠的两种最常见和最严重的并发症有关,即孕妇先兆子痫 (PE) 和胎儿宫内生长受限 (IUGR),每种疾病影响约 5% 的妊娠。使用小鼠作为研究人类疾病的模型的一个重要问题是从人到小鼠的遗传控制途径的功能保守程度。人类和小鼠胎盘显示出结构相似性,但还没有系统地尝试评估它们的分子相似性或差异。我们通过鸟枪蛋白质组学和对从人类和小鼠近期胎盘中显微解剖的高度血管交换区域进行微阵列表达分析,收集了蛋白质和 mRNA 表达数据。检测到超过 7000 个直系同源基因,其中 70% 在两个物种中共表达。我们的人类蛋白质组学结果与人类蛋白质图谱中通过免疫组织化学分析的人类胎盘表达的 1649 个基因之间存在接近 90% 的一致性。有趣的是,超过 80% 的已知导致小鼠胎盘表型的基因在人类中共表达。其中一些与表型相关的蛋白质形成了一个紧密的蛋白质-蛋白质相互作用网络,涉及 15 种已知蛋白质和 34 种新候选蛋白质,这些蛋白质也可能对胎盘结构和/或功能很重要。整个数据可作为可通过网络访问的数据库提供,以指导小鼠模型的知情开发以研究人类疾病。
Placental abnormalities are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ∼5% of all pregnancies. An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities, but there have been no systematic attempts to assess their molecular similarities or differences. We collected protein and mRNA expression data through shot-gun proteomics and microarray expression analysis of the highly vascular exchange region, microdissected from the human and mouse near-term placenta. Over 7000 ortholog genes were detected with 70% co-expressed in both species. Close to 90% agreement was found between our human proteomic results and 1649 genes assayed by immunohistochemistry for expression in the human placenta in the Human Protein Atlas. Interestingly, over 80% of genes known to cause placental phenotypes in mouse are co-expressed in human. Several of these phenotype-associated proteins form a tight protein–protein interaction network involving 15 known and 34 novel candidate proteins also likely important in placental structure and/or function. The entire data are available as a web-accessible database to guide the informed development of mouse models to study human disease.
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