Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global transcriptional analysis of S. mutans metalloregulation

ABSTRACT: Multiple S. mutans genes that are subject to SloR control are likely contributors to virulence. The regulation of these genes in response to metal ion limitation vs. availability in the oral cavity can significantly facilitate the caries-forming process and hence continued analysis of these data can reveal novel candidate genes for the purposes of therapeutic intervention and/or prevention. Keywords: Genetic modification, dose response, metalloregulation Analyses were based on a comparison between low Mn and high Mn groups (paired comparisons A, B, and C) and the monitoring of gene expression in the presence (WT) or absence (mutant) of SloR under moderate Mn content. Analysis of significance amongst all genes and the formulation of hypotheses that are relevant to the cariogenic state were performed.

ORGANISM(S): Streptococcus mutans UA159

SUBMITTER: Jeffrey Bond

PROVIDER: E-GEOD-10215 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary.

Dunning Daniel W DW McCall Lathan W LW Powell William F WF Arscott W Tristram WT McConocha Erin M EM McClurg Cheryl J CJ Goodman Steven D SD Spatafora Grace A GA

Microbiology (Reading, England) 20080401 Pt 4

Streptococcus mutans, the primary causative agent of human dental caries, grows as a biofilm on the tooth surface, where it metabolizes dietary carbohydrates and generates acid byproducts that demineralize tooth enamel. A drop in plaque pH stimulates an adaptive acid-tolerance response (ATR) in this oral pathogen that allows it to survive acid challenge at pHs as low as 3.0. In the present study, we describe the growth of an S. mutans mutant, GMS901, that harbours an insertion-deletion mutation ...[more]

PMID: 18375805

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Project description:Single cell transcriptomic analyses (scRNAseq) of hepatocytes and liver endothelial cells (L-EC) have revolutionized the understanding of the spatial architecture of liver structure and function. The spatial alignment of L-EC and hepatocytes is pivotal for liver function in health and disease given that L-EC act as instructive gatekeeper of nearby hepatocytes including the maintenance of liver metabolic zonation in a Wnt-dependent manner. Advancing liver biology beyond the ’transcript-centric’ view of scRNAseq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyse post-translational modifications. Here, by combining spatial cell sorting methodology with transcriptomic and quantitative proteomic/phospho-proteomic analyses, we established the first functionally and spatially-resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signalling mechanisms. Phosphorylation of receptor tyrosine kinases (RTK) was detected preferentially in the central vein area resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation of the identified strong phosphorylation gradient of the vascular RTK Tie1 by blockade resulted in the rapid peri-central dysregulation of the L-EC transcriptome. Notably, the expression of Wnt9b in L-EC was discovered as Tie receptor controlled with reciprocal regulation by FoxO1 and STAT3 transcription factors. Genetic inactivation of Tie1 in L-EC or antibody blockade resulted in reduced liver regeneration following partial hepatectomy with reduced Wnt ligand and Wnt target gene expression, including Axin2, Sox9, Tbx3 and Lgr5. Taken together, the study has yielded unparalleled insight into the spatial organization of L EC signalling and discovered a vascular Tie-Wnt signalling axis as regulator of liver function. The employed spatial sorting technique followed by phospho-proteomic analysis may be employed as a universally adaptable strategy for the spatial phosphoproteomic analysis of scRNAseq data-defined relevant cellular (sub)-populations.

Dataset Information

Global transcriptional analysis of S. mutans metalloregulation

Publications

SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary.

Similar Datasets

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