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Multiple genome analyses reveal key genes in Vitamin C and Vitamin D synthesis and transport pathways are shared.

ABSTRACT: Vitamin C (VC) and vitamin D (VD) have been widely used as the dietary supplements and in treatment of diseases both independently and in combination. Whether there is a connection between their pathways is critical for their therapeutic applications. Using whole-genome expression profiles, we performed multiple measures of associations, networks, eQTL mappings and expressions of key genes of interest in VC and VD functions. Several key genes in their pathways were found to be associated. Gc and Rgn play important roles connecting VC and VD pathways in mice. The r values of expression levels between Gc and Rgn in mouse spleen, liver, lung, and kidney are 0.937, 0.558, 0.901, and 0.617, respectively. The expression QTLs of Gc and Rgn are mapped onto the same locations, i.e., 68-76 MB in chromosome 7 and 26-36 MB in chromosome 9. In humans, there are positive correlations between CYP27B1 and SLC23A1 expression levels in kidney (r?=?0.733) and spleen (r?=?0.424). SLC23A2 and RXRA are minimally associated in both mouse and human. These data indicate that pathways of VC and VD are not independent but affect each other, and this effect is different between mice and humans during VC and VD synthesis and transportation.

SUBMITTER: Dong W

PROVIDER: S-EPMC6856197 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Multiple genome analyses reveal key genes in Vitamin C and Vitamin D synthesis and transport pathways are shared.

Dong Wei W Tian Cheng C Jiao Yan Y Blackwell Savannah S Lou Ge G Postlethwaite Arnold A Gu Weikuan W Sun Dianjun D

Scientific reports 20191114 1

Vitamin C (VC) and vitamin D (VD) have been widely used as the dietary supplements and in treatment of diseases both independently and in combination. Whether there is a connection between their pathways is critical for their therapeutic applications. Using whole-genome expression profiles, we performed multiple measures of associations, networks, eQTL mappings and expressions of key genes of interest in VC and VD functions. Several key genes in their pathways were found to be associated. Gc and ...[more]

PMID: 31727908

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Project description:INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models.

Project description:BackgroundAlzheimer's disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.MethodsGene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree?10 (for hippocampus tissues) and???8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA).Results251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD.ConclusionsThrough GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.

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Multiple genome analyses reveal key genes in Vitamin C and Vitamin D synthesis and transport pathways are shared.

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Multiple genome analyses reveal key genes in Vitamin C and Vitamin D synthesis and transport pathways are shared.

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