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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human control (hMSC-TERT) vs Dlk overexpressing cells (hMSC-Dlk1) to analyse Dlk1-mediated signaling pathways during hMSC differentiation

ABSTRACT: We aimed in this study to identify the differentially regulated genes by Dlk1 in hMSC cells using microarray technology in order to gain a better understanding of Dlk1-mediated signaling pathways during hMSC differentiation. Both control (hMSC-TERT)(not expressing Dlk1) and Dlk1 overexpressing cells (hMSC-Dlk1) were cultured in triplicate at 3×104 cells/cm2 in Petri-dish in standard growth medium. At 90-100% confluence, highly purified total cellular RNA was isolated from each of three independent cultures per cell line using RNeasy Kit (QIAGEN Nordic, West Sussex, UK) according to the manufacturer?s instructions

ORGANISM(S): Homo sapiens

SUBMITTER: Jesper Dahlgaard

PROVIDER: E-MEXP-560 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors.

Abdallah Basem M BM Boissy Patrice P Tan Qihua Q Dahlgaard Jesper J Traustadottir Gunnhildur A GA Kupisiewicz Katarzyna K Laborda Jorge J Delaisse Jean-Marie JM Kassem Moustapha M

The Journal of biological chemistry 20061219 10

dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpr ...[more]

PMID: 17182623

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DLK1 Is a Novel Regulator of Bone Mass That Mediates Estrogen-Deficiency Induced Bone Loss in Mice

Project description:DLK1/FA-1 (delta-like 1/fetal antigen-1) is a transmembrane protein belonging to Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here, we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific-Dlk1 over-expressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). Î¼CT-scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone formation rate and enhanced bone resorption in Col1-Dlk1 as compared to WT. At a cellular level, DLK1 markedly reduced the total number of bone marrow (BM)-derived CFU-F, as well as their osteogenic capacity. In a number of in vitro culture systems, DLK1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of pro-inflammatory bone resorbing cytokines (e.g, Il7, Tnfa and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of DLK1 in bone marrow by activated T-cells. However, Dlk1-/- mice were protected from ovx-induced bone loss. Thus, we identified DLK1 as a novel regulator of bone mass that function to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T-cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss. Calvarial osteoblasts were grown from neonatal mice overexpressing Dlk1 and their non-transgenic littermate controls. Three separate cultures from each of the two genotypes were combined and analysed by Affymetrix microarray MOE430 2.0.

2010-10-15 | E-GEOD-22113 | biostudies-arrayexpress

microRNA expression profiling during Adipocytic differentiation of human MSCs (hMSC-TERT)

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2015-06-23 | E-GEOD-70103 | biostudies-arrayexpress

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2014-09-09 | E-GEOD-59458 | biostudies-arrayexpress

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma

Project description:Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, the often fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma. Plasma membrane-enriched mass spectrometry identified 1,461 cell surface proteins in cell lines and 1,401 in xenograft models, respectively. Additional proteogenomic analyses revealed 71 high-confidence candidate immunotherapeutic targets and we prioritized Delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlated with the presence of a super-enhancer spanning the DLK1 locus. Robust cell surface expression of DLK1 was validated by immunofluorescence, flow cytometry, and immunohistochemistry. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells resulted in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), showed potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Finally, we also found that DLK1 is highly expressed in several adult cancer types including adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PCPG) and small cell lung cancer (SCLC) suggesting potential clinical benefit beyond neuroblastoma. A clinical trial has been developed for evaluating ADCT-701 in neuroendocrine tumors in adults (https://www.clinicaltrials.gov/study/NCT06041516?term=adct-701&rank=1). Therefore, comprehensive characterization of cancer surfaceomes can provide biologically relevant immunotherapy targeting strategies.

2024-10-23 | PXD047474 | Pride

Transcription profiling of human mesenchymal stem cells transfected with adenoviruses carrying the SOX trio or LacZ control to identify target molecules

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2007-04-01 | E-MEXP-960 | biostudies-arrayexpress

Data expression of young and senescent human mesenchymal stem cells (hMSC).

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Single cell RNAseq data from Dlk1+ and Dlk1- aged murine hematopoietic stem cells

Project description:Quantification of gene expression noise on young versus aged bone marrow HSCs at single-cell resolution revealed Dlk1 increases both noise and expression levels upon aging. Dlk1, encoding a cell surface non-canonical Notch ligand, is partially expressed in the LT-HSC compartment, without generating clusters of individual subpopulations by conventional clustering analysis. We aimed to characterize the trascriptome of aged LT-HSC with positive and negative expression of Dlk1 cells. Dataset created as part of the publication: "VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells"

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2016-09-01 | GSE83901 | GEO

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