Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development.
Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development.
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DOI：
10.1186/s12864-016-3216-y
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发表时间：
2016-11-03
期刊：
影响因子：
4.4
通讯作者：
Schook LB
中科院分区：
文献类型：
--
作者：
Schachtschneider KM;Liu Y;Rund LA;Madsen O;Johnson RW;Groenen MA;Schook LB
缺铁是一种常见的儿童微量营养素缺乏症，可导致海马功能改变和认知障碍。然而，很少有人知道通过新生儿缺铁导致海马基因表达和功能的长期持久的改变的机制。DNA甲基化是一种表观遗传标记，参与基因调控，并受环境因素的影响。在这项研究中，海马DNA甲基化和基因表达通过减少代表性亚硫酸氢盐测序和RNA-seq对来自先前研究的样本进行评估，该研究报告了新生儿缺铁的猪生物医学模型中基于海马的学习和记忆减少。在总共192差异表达基因（DEG）之间的铁缺乏和对照组进行了鉴定。GO术语和途径富集分析鉴定了与缺氧、血管生成、血脑屏障（BBB）通透性增加以及神经发育和功能改变相关的DEG。特别令人感兴趣的是先前与人类和小鼠的认知缺陷和行为障碍有关的基因，包括HTR 2A、HTR 2C、PAK 3、PRSS 12和NETO 1。在50万个CpG和240万个非CpG位点上观察到全基因组DNA甲基化的改变。在组间总共鉴定了853个差异甲基化（DM）CpG和99个DM非CpG位点。当比较DM非CpG位点时，样品按组聚类，表明响应于新生儿环境的非CpG甲基化的高度保守性。总共12个DM位点与9个DEG相关，包括参与血管生成、神经发育和神经元功能的基因。新生儿缺铁导致海马DNA甲基化和基因调控改变，参与缺氧、血管生成、血脑屏障通透性增加以及神经发育和功能改变。总之，这些结果为新生儿缺铁导致人类认知发育长期持续下降的机制提供了新的见解。本文的在线版本（doi：10.1186/s12864-016-3216-y）包含补充材料，可供授权用户使用。
Iron deficiency is a common childhood micronutrient deficiency that results in altered hippocampal function and cognitive disorders. However, little is known about the mechanisms through which neonatal iron deficiency results in long lasting alterations in hippocampal gene expression and function. DNA methylation is an epigenetic mark involved in gene regulation and altered by environmental factors. In this study, hippocampal DNA methylation and gene expression were assessed via reduced representation bisulfite sequencing and RNA-seq on samples from a previous study reporting reduced hippocampal-based learning and memory in a porcine biomedical model of neonatal iron deficiency. In total 192 differentially expressed genes (DEGs) were identified between the iron deficient and control groups. GO term and pathway enrichment analysis identified DEGs associated with hypoxia, angiogenesis, increased blood brain barrier (BBB) permeability, and altered neurodevelopment and function. Of particular interest are genes previously implicated in cognitive deficits and behavioral disorders in humans and mice, including HTR2A, HTR2C, PAK3, PRSS12, and NETO1. Altered genome-wide DNA methylation was observed across 0.5 million CpG and 2.4 million non-CpG sites. In total 853 differentially methylated (DM) CpG and 99 DM non-CpG sites were identified between groups. Samples clustered by group when comparing DM non-CpG sites, suggesting high conservation of non-CpG methylation in response to neonatal environment. In total 12 DM sites were associated with 9 DEGs, including genes involved in angiogenesis, neurodevelopment, and neuronal function. Neonatal iron deficiency leads to altered hippocampal DNA methylation and gene regulation involved in hypoxia, angiogenesis, increased BBB permeability, and altered neurodevelopment and function. Together, these results provide new insights into the mechanisms through which neonatal iron deficiency results in long lasting reductions in cognitive development in humans. The online version of this article (doi:10.1186/s12864-016-3216-y) contains supplementary material, which is available to authorized users.
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影响因子：
25
作者：
Guo, Junjie U.;Su, Yijing;Shin, Joo Heon;Shin, Jaehoon;Li, Hongda;Xie, Bin;Zhong, Chun;Hu, Shaohui;Le, Thuc;Fan, Guoping;Zhu, Heng;Chang, Qiang;Gao, Yuan;Ming, Guo-li;Song, Hongjun
通讯作者：
Song, Hongjun
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Boda, B;Alberi, S;Muller, D
通讯作者：
Muller, D
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily