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RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes
The Journal of Nutritional Biochemistry ( IF 5.6 ) Pub Date : 2021-07-06 , DOI: 10.1016/j.jnutbio.2021.108814
Zhi Chai 1 , Yafei Lyu 2 , Qiuyan Chen 3 , Cheng-Hsin Wei 3 , Lindsay M Snyder 4 , Veronika Weaver 4 , Aswathy Sebastian 5 , István Albert 6 , Qunhua Li 7 , Margherita T Cantorna 4 , A Catharine Ross 3
Affiliation  

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.



中文翻译:

RNAseq 研究揭示了小肠与结肠对维生素 A 缺乏症的不同转录反应,揭示了新的维生素 A 调节基因

在资源有限的地区,维生素 A (VA) 缺乏症仍然普遍存在。使用柠檬酸杆菌作为腹泻病模型的小鼠感染,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率和存活率降低。为了表征先前存在的 VA 缺乏对肠道基因表达模式的影响,并在 VA 相关的生物学途径中发现新的靶基因,饮食诱导了小鼠的 VA 缺乏。从小肠 (SI) 和结肠中提取总 mRNA,并进行测序。进行了差异表达基因 (DEG)、基因本体论 (GO) 富集和共表达网络分析。VAS 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 在与类视黄醇代谢过程、分子结合和免疫功能相关的类别中显着富集。三个共表达模块与 SI 中的 VA 状态显着相关;这些模块包含四个已知的视黄酸目标。此外,其他感兴趣的 SI 基因(例如,这些模块中的Mbl2、Cxcl14Nr0b2)被认为是受 VA 调节的新候选基因。此外,我们的分析表明,SI 中两种细胞类型的标记,肥大细胞和簇绒细胞,因 VA 状态而显着改变。在结肠中,“细胞分裂”是唯一丰富的类别,与 VA 呈负相关。因此,这些数据表明 SI 和结肠在饮食 VA 的调节下具有不同的网络,并且预先存在的 VA 缺乏可能对宿主对各种疾病状况的反应产生重大影响。

更新日期:2021-07-30
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