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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human coronary artery smooth muscle treated with vitamin D sterol

ABSTRACT: Chondro/osteoblastic and cardiovascular-disease associated genes are modulated in human coronary artery smooth muscle cells that calcify in the presence of phosphate and vitamin D sterols. Looking at the effect of media conditions with and without Vitamin D, paracalcitriol (a vitamin D analog), or R568 (a calcimimetic) vs. dose and time on calcification of human coronary smooth muscle cells. Experiment Overall Design: CASMCs were exposed to differentiation medium [beta glycerophosphate (10 mM), ascorbic acid (50 mg/ml), and dexamethasone (10-9 M) with and without calcitriol or paricalcitol (10-8 M) for 7 days, and total RNA was examined by microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: Lori Twehues

PROVIDER: E-GEOD-11917 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Vitamin D sterol effects on coronary ASMC genes

Project description:Chondro/osteoblastic and cardiovascular-disease associated genes are modulated in human coronary artery smooth muscle cells that calcify in the presence of phosphate and vitamin D sterols. Looking at the effect of media conditions with and without Vitamin D, paracalcitriol (a vitamin D analog), or R568 (a calcimimetic) vs. dose and time on calcification of human coronary smooth muscle cells.

2008-06-28 | GSE11917 | GEO

Antagonistic interaction between androgen signaling and vitamin D signaling in prostate cancer [ChIP-Seq]

Project description:Vitamin D induces anti-proliferative and differentiating effects in prostate cancer. Thus calcitriol, the hormonally active form of Vitamin D, and its analogs have been extensively studied in prostate cancer cells. Yet despite its importance, relatively little is known about the genome-scale mechanisms by which Vitamin D, through its cognate nuclear vitamin D receptor (VDR), exerts its regulatory functions at the genomic level. In this study, we defined VDR transcriptional networks in the LNCaP prostate cancer cell line by mapping the genomic binding sites of VDR and by identifying differentially expressed genes upon calcitriol treatment. We found that VDR and androgen receptor (AR) antagonistically regulate a subset of cell cycle-related genes that are over-expressed in prostate cancer tumors. The expression balance of these genes is partially regulated through the competition dynamics between AR and VDR binding to shared cis-regulatory elements. On such shared elements, we found that FOXA1 mediates this competition by serving as a pioneering factor for both AR and VDR binding. We also found significant enrichment of AR-, VDR-, and AR/VDR overlapping binding sites in prostate cancer-associated single-nucleotide polymorphism (SNP) intervals identified from genome-wide association studies (GWAS), providing genetic evidence to link AR, VDR and their crosstalk to prostate cancer susceptibilities. In particular, we found that in a cis-regulatory element of the RFX6 gene implicated in prostate cancer progression, an allelic variant increases prostate cancer risk by switching the antagonism between AR and VDR into a synergistic interaction. Examination of AR, VDR, and FOXA1 binding in LNCaP cells, in biological replicates

2015-08-01 | E-GEOD-64656 | biostudies-arrayexpress

Genome-wide Analysis of Vitamin D Receptor Binding By ChIP-Seq

Project description:We used ChIP-Seq to identify the genomic locations bound by the vitamin D receptor (VDR) in two lymphoblastoid cell lines (LCLs) (CEPH individuals GM10855 and GM10861 from the International HapMap Project) before and after calcitriol treatment for 36 hours. Immunoprecipitated DNA was sequenced using the Illumina Genome Analyzer II. Sequence reads (35 bases; 10-19 million quality-filtered reads/sample) were aligned to the human genome (NCBI Build 36.3) using ELAND software. The number of unique alignments ranged from 7.73 million to 14.32 million. Peaks were called in the aligned sequence data using a model-based analysis of ChIP-Seq (MACS) and compared with sequenced sonicated and amplified input DNA. In the samples not treated with calcitriol, the number of peaks ranged from 468 to 4538 (median 975, mean 1587), while in the calcitriol-treated samples the number of peaks was between 2560 and 7244 (median 4546, mean 4560). 65-75% of peaks of untreated samples were in promoters, while only 24-50% of peaks of calcitirol-treated samples were in promoters. This study provides a comprehensive map of VDR binding in lymphoblastoid cell lines. The GM10855 and GM10861 cell lines were either stimulated for 36 hours with calcitriol or unstimulated, and crosslinked with formaldehyde to generate a snapshot of all protein-DNA interactions occurring in the nucleus at that particular point in time. Antibodies were then used to immunoprecipitate the VDR protein together with the crosslinked DNA fragments. Following reversal of crosslinks and digestion of protein, adaptors were ligated to immunoprecipitated DNA, and bridge PCR was used to generate clonally amplified amplicons before sequencing by synthesis using the Illumina Solexa Genome Analyzer.

2010-06-22 | E-GEOD-22484 | biostudies-arrayexpress

Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells

Project description:Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial (EC) and vascular smooth muscle cells (SM). At present, it is unclear whether the cell fate program of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field (SHF) cardiovascular progenitors (CVPs) using WNT3A and Endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1+ vascular intermediates, and demonstrates for the first time, the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo. The HumanHT-12 v4 BeadChip (Illumina) was used to analyse paracrine factors produced by sub-regions of the fetal heart, followed by pairing the paracrine factors present in these specific regions with corresponding receptors that are highly expressed in uncommitted cardiovascular progenitor cells.

2015-12-15 | E-GEOD-75985 | biostudies-arrayexpress

The Histone H2B Monoubiquitination Regulatory Pathway is Required for Differentiation of Multipotent Stem Cells

Project description:Extensive changes in post-translational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs), various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSC. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSC cells and plays a central role in controlling stem cell differentiation. This set contains 29 microarray samples and includes the following 5 conditions: undifferentiated hMSCs, 2 day osteoblast differentiation, 5 day osteoblast differentiation, 2 day adipocyte differentiation, and 5 day adipocyte differentiation. 3 siRNA control samples and 3 RNF40 knockdown samples for each condition (except two control siRNA samples for 2 days osteoblast differentiation).

2013-01-03 | E-GEOD-38173 | biostudies-arrayexpress

Gene expression profile of human monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25a-dihydroxyvitamin D3 (1,25D3)

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2013-12-31 | E-GEOD-46268 | biostudies-arrayexpress

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2010-11-15 | E-GEOD-23984 | biostudies-arrayexpress

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2010-12-11 | E-GEOD-19441 | biostudies-arrayexpress

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