Similar Datasets
Project description:ChIP-seq of beta-catenin and TCF4 in mouse marrow derived MSCs
| PRJNA564532 | ENA
Project description:β-catenin signaling can be both a physiological and an oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20 to 40% of hepatocellular carcinomas with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by Tcf4 and β-catenin, their transcriptome and their metabolome. We find that Tcf4 DNA-bindings depend on β-catenin. Tcf4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf4 on Hnf4-responsive elements. β-catenin, Tcf4 and Hnf4α interact, dictating β-catenin transcription which is antagonistic to that elicited by Hnf4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. We conclude that β-catenin patterns the zonal liver together with Tcf4, Hnf4α and xenobiotic nuclear receptors. This network represses lipid metabolism, and exacerbates glutamine, drug and bile metabolism, mirroring hepatocellular carcinomas with β-catenin mutational activation. In vivo liver samples in 4 conditions: Betacat activated (WCE, Tcf4 chipseq, Betacat chipseq, mRNAseq with 2 replicates), Betacat null (WCE, Tcf4 chipseq, mRNAseq with 2 replicates), Betacat control (mRNAseq with 2 replicates), Wild type (mRNAseq with 2 replicates)
2014-01-18 | E-GEOD-35213 | biostudies-arrayexpress
Project description:β-catenin signaling can be both a physiological and an oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20 to 40% of hepatocellular carcinomas with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by Tcf4 and β-catenin, their transcriptome and their metabolome. We find that Tcf4 DNA-bindings depend on β-catenin. Tcf4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf4 on Hnf4-responsive elements. β-catenin, Tcf4 and Hnf4α interact, dictating β-catenin transcription which is antagonistic to that elicited by Hnf4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. We conclude that β-catenin patterns the zonal liver together with Tcf4, Hnf4α and xenobiotic nuclear receptors. This network represses lipid metabolism, and exacerbates glutamine, drug and bile metabolism, mirroring hepatocellular carcinomas with β-catenin mutational activation.
2014-01-18 | GSE35213 | GEO
Project description:Many of the transcriptional and growth regulating activities of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the intestine and colon are recapitulated in the human colorectal cancer cell LS180. We therefore used this line together with ChIP-seq and gene expression analyses to identify the vitamin D receptor (VDR)/retinoid x receptor (RXR) and TCF7L2(TCF4)/β-catenin cistromes and the genes that they regulate. VDR and RXR co-localized to predominantly promoter distal, VDRE-containing sites in a largely ligand-dependent manner. These regulatory sites control the expression of both known as well as novel 1,25(OH)2D3 target genes. TCF4 and β-catenin cistromes partially overlapped, contained TCF/LEF consensus elements, and were only modestly influenced by 1,25(OH)2D3. However, the two heterodimer complexes co-localized at sites near a limited set of genes that included c-FOS and c-MYC; the expression of both genes was modulated by 1,25(OH)2D3. At the c-FOS gene, both VDR/RXR and TCF4/β-catenin bound to a single distal enhancer located 24 kb upstream of the transcriptional start site. At the c-MYC locus, however, binding was noted at a cluster of sites between -139 and -165 kb and at a site located -335 kb upstream. Examined as isolated enhancer fragments, these regions exhibited basal and 1,25(OH)2D3-inducible activities that were interlinked to both VDR and β-catenin activation. These data reveal additional complexity in the regulation of target genes by 1,25(OH)2D3 and support a direct action of both VDR and the TCF4/β-catenin regulatory complex at c-FOS and c-MYC.
2011-11-22 | GSE31939 | GEO
Project description:MicroRNA Expression in Bone Marrow-Derived Human MSCs
| PRJNA344026 | ENA
Project description:The lineage commitment and differentiation of mesenchymal stem cells (MSCs) play a crucial role in the maintenance of bone stability. MAPK7 (Mitogen-activated protein kinase 7), a member of the MAPK family, controls cell proliferation, differentiation, and survival. However, the specific role of Mapk7 in regulating the osteogenic and adipogenic differentiation of MSCs remains to be determined. In this study, depletion of Mapk7 in MSCs (Prx1-Cre) resulted in severe low bone mass and accumulation of bone marrow fat in mice exhibiting osteoporosis. In vitro, overexpression of Mapk7 in MSCs induced an enhancement of osteogenesis in MSCs, while adipogenesis was attenuated. Mechanistically, MAPK7 availed to influence the activity of WNT/β-catenin signaling by modulating the phosphorylation of LRP6 ser1490, which ultimately impacted the osteogenic-adipogenic differentiation fate of MSCs for the first time. This is of great clinical and scientific significance for understanding the biological function of Mapk7 gene and developing new therapeutic targets for OP. Our study for the first time demonstrates that Mapk7/Lrp6/β-catenin signal axis plays a critical role in regulating the osteogenic and adipogenic differentiation of MSCs. It also suggests that modulating the function of Mapk7 may benefit the treatment of MSCs differentiation inbalance related bone diseases such as osteoporosis.
2024-02-15 | GSE255596 | GEO
Project description:Primary human bone marrow-derived mesenchymal stem cells (MSCs) were treated with recombinant human TGFb1 (10ng/ml) for different time points (1, 3, 7, 14, 24 hours)
2017-04-28 | E-MTAB-5420 | biostudies-arrayexpress
Project description:Primary human bone marrow-derived mesenchymal stem cells (MSCs) were treated with recombinant human TNFa (50ng/ml) for different time points (1, 3, 7, 14, 24 hours)
2017-04-28 | E-MTAB-5421 | biostudies-arrayexpress
Project description:Mesenchymal stromal cells (MSCs) are located in bone marrow where they help to maintain bone homeostasis and repair through the ability to expand in response to mitotic stimuli and differentiate into skeletal linages. The signalling mechanisms that enable precise control of MSC function remain unclear. Here, we have identified a non-canonical epidermal growth factor (EGF) signalling pathway in MSCs, which acts via integrin-linked kinase (ILK) to activate β-catenin, a key component of Wnt signalling. EGF induces nuclear translocation of β-catenin in MSCs but does not drive T cell factor (TCF)-mediated transactivation of Wnt target genes, and we demonstrate by Design of Experiments statistical analysis that the EGF/β-catenin and Wnt/β-catenin pathways do not cross-talk following co-stimulation with multiple concentrations of both ligands. By examining EGF-regulated genes in MSCs by RNA-Sequencing, we identified gene sets that were exclusively regulated by the EGF/b-catenin pathway, which were distinct from canonical EGF-regulated genes. In contrast, the expression of subsets of canonical EGF signalling gene targets were significantly influenced by b-catenin activation. These newly-identified EGF signalling pathways cooperate to enable EGF-mediated proliferation of MSCs by alleviating the suppression of cell cycle pathways induced by canonical EGF signalling.
2018-10-24 | GSE121697 | GEO
Project description:Early osteoinductive bone marrow MSCs (e-MSCs) acquire enhanced hematopoiesis-supportive ability. We performed microarray analysis on e-MSCs. Cell chemotaxis-assosiated genes were positively enriched and cell adhesion-associated genes were negatively enriched compared with control MSCs. The expression of CXCL12 and VCAM1 extremely decreased.
2015-11-27 | GSE74837 | GEO