RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes.
RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes.
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DOI：
10.1016/j.jnutbio.2021.108814
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发表时间：
2021-12
期刊：
影响因子：
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通讯作者：
Ross AC
中科院分区：
文献类型：
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作者：
Chai Z;Lyu Y;Chen Q;Wei CH;Snyder LM;Weaver V;Sebastian A;Albert I;Li Q;Cantorna MT;Ross AC
维生素A缺乏症在资源有限的地区仍然普遍存在。使用啮齿类柠檬酸杆菌感染小鼠作为肠道疾病的模型，先前的报告显示由于维生素A缺乏（VAD）状态导致病原体清除和存活减少。为了表征预先存在的VA缺乏对肠道中基因表达模式的影响，并发现VA相关生物学途径中的新靶基因，通过饮食诱导小鼠中的VA缺乏。从小肠（SI）和结肠提取总mRNA，并测序。进行差异表达基因（DEG）、基因本体（GO）富集和共表达网络分析。VAS组和VAD组之间的DEG比较检测到49个SI和94个结肠基因。通过GO信息，SI DEG在与类维生素A代谢过程、分子结合和免疫功能相关的类别中显著富集。三个共表达模块显示出显着的相关性与VA状态SI，这些模块包含四个已知的视黄酸目标。此外，其他感兴趣的S1基因（例如，Mbl2、Cxcl14和Nr0b2）可能是VA调控的新的候选基因。此外，我们的分析表明，标志物的两种细胞类型的SI，肥大细胞和簇细胞，VA状态显着改变。在结肠中，“细胞分裂”是唯一富集的类别，与VA呈负相关。因此，这些数据表明，SI和结肠有不同的网络下的饮食VA的调节，和预先存在的VA缺乏可能有显着影响宿主对各种疾病的反应。
Vitamin A (VA) deficiency remains prevalent in resource limited areas. Using Citrobacter rodentium infection in mice as a model for diarrheal diseases, previous reports showed reduced pathogen clearance and survival due to vitamin A deficient (VAD) status. To characterize the impact of preexisting VA deficiency on gene expression patterns in the intestines, and to discover novel target genes in VA-related biological pathways, VA deficiency in mice were induced by diet. Total mRNAs were extracted from small intestine (SI) and colon, and sequenced. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and co-expression network analyses were performed. DEGs compared between VAS and VAD groups detected 49 SI and 94 colon genes. By GO information, SI DEGs were significantly enriched in categories relevant to retinoid metabolic process, molecule binding, and immune function. Three co-expression modules showed significant correlation with VA status in SI; these modules contained four known retinoic acid targets. In addition, other SI genes of interest (e.g., Mbl2, Cxcl14, and Nr0b2) in these modules were suggested as new candidate genes regulated by VA. Furthermore, our analysis showed that markers of two cell types in SI, mast cells and Tuft cells, were significantly altered by VA status. In colon, “cell division” was the only enriched category and was negatively associated with VA. Thus, these data suggested that SI and colon have distinct networks under the regulation of dietary VA, and that preexisting VA deficiency could have a significant impact on the host response to a variety of disease conditions.