Project description:Intestinal organoids are a good model of in vitro tissue regeneration that faithfully recapitulates majority of cell types of the intestine. To analyze the impact of LXR activation in intestinal regeneration and overall cellular composition, organoids established from WT mice were treated with either vehicle (DMSO) or GW3965 and were analyzed using 10X scRNAseq platform.
Project description:Liver X Receptor (LXR) activation in intestinal epithelial organoids promotes their growth in vitro. To investigate the downstream effect of LXR activation in intestinal epithelial cells and identify potential pathways driving regeneration, we carried out an unbiased transcriptomic analysis of intestinal epithelial organoids stimulated with the LXR agonist GW3965. In detail, wild type small intestinal crypts were seeded in vitro and stimulated with vehicle (DMSO) or GW3965. After six hours, closing crypts (organoids) were collected for RNA extraction and were analyzed by RNA sequencing.
Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes
Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes AML-12 cells co-treated with 0.75mM PA+/- 10µM GW3965 for 24 h +/- Ulk1 SiRNA
Project description:Generation of high density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most HDL in blood, small intestines also can synthesize HDL. However, distinct functions for intestinal HDL are unknown. Here we designed intestine-specific activation of LXR via low-dose administration of GW3965, LXR agonist. The liver status was improved by therapeutics that elevated and depended upon intestinal HDL production via GW3965. Thus, protection of the liver from injury in response to gut-derived signals like LPS is a major function of intestinally synthesized HDL.
Project description:We used RNA-sequencing to determine the transcriptional response to liver X receptor (LXR) activation in primary human CD4+ T cells, both at rest and under activation conditions. CD4+ T cells were isolated from 3 healthy donors and treated with the synthetic LXR agonist GW3965 (GW) for 24 hours. Gene expression was compared to control samples (CTRL) treated with the LXR antagonist GSK1440233. To activate the T cell antigen receptor (TCR), cells were pre-treated with CTRL/GW alone for 6 hours then transferred to plates containing anti-CD3 and anti-CD28 for a further 18 hours.
Project description:We investigated mechanisms by which LXRs regulate midbrain dopaminergic neuron development. Using a systems biology approach, we found that LXR interacts with β-catenin and that LXR activation inhibits the activity of the Wnt/β-catenin pathway
Project description:Cell invasion and metastasis is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through differing and complex 3D extracellular environments. In this study we set out to identify the parameters required for invasive cell migration in 3D environments. Cells interact with the extracellular matrix via transmembrane-spanning integrin adhesion complexes. We establish a technique to determine the composition of cell-matrix adhesion complexes in invasive breast cancer cells in 3D matrices and on 2D surfaces and identify an interaction complex that is enriched in 3D adhesion sites and required for invasive migration.
Project description:We investigated mechanisms by which LXRs regulate midbrain dopaminergic neuron development. Using a systems biology approach, we found that LXR interacts with β-catenin and that LXR activation inhibits the activity of the Wnt/β-catenin pathway
