Quantification of vascular lineage-specific differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE11308 | GEO | 2008/10/04
SECONDARY ACCESSION(S): PRJNA106615
REPOSITORIES: GEO
Similar Datasets
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. This SuperSeries is composed of the following subset Series: GSE11306: Quantification of vascular lineage-specific differentiation (cell type comparison) GSE11307: Quantification of vascular lineage-specific differentiation, psoriasis (chronic inflammation) study Keywords: SuperSeries Refer to individual Series
2008-10-04 | E-GEOD-11308 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, psoriasis (chronic inflammation) study Guided by the gene array results, we selected 54 LEC-specific genes and 31 BEC-specific genes, based upon their consistent and strong specific expression in LEC or BEC, as well as on their assignment to important biological pathways. In addition, the five pan-endothelial cell marker genes PECAM-1, vWF, KDR, TEK, CDH5 and the six endogenous control genes ACTB, GAPDH, PGK1, PPIA, RPLP0 and S18 were included in the design of the LD-MDA. After extraction of total RNA, the mRNA expression levels of the 96 genes were analyzed by quantitative RT-PCR using the 7900HT Real-Time PCR System (Applied Biosystems).
2008-10-04 | E-GEOD-11307 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: cell type comparison
2011-04-01 | GSE6549 | GEO
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, cell type comparison Guided by the gene array results, we selected 54 LEC-specific genes and 31 BEC-specific genes, based upon their consistent and strong specific expression in LEC or BEC, as well as on their assignment to important biological pathways. In addition, the five pan-endothelial cell marker genes PECAM-1, vWF, KDR, TEK, CDH5 and the six endogenous control genes ACTB, GAPDH, PGK1, PPIA, RPLP0 and S18 were included in the design of the LD-MDA. The LD-MDA was then used to evaluate the lineage-specific differentiation of a total of 10 independent lines of primary human dermal LEC, of 8 independent lines of primary human dermal BEC, of two independent lines of HUVEC cells, of the immortalized human microvascular endothelial cell line HMEC-1, of the immortalized human epidermal keratinocyte line HaCaT, and of primary human dermal fibroblasts. After extraction of total RNA, the mRNA expression levels of the 96 genes were analyzed by quantitative RT-PCR using the 7900HT Real-Time PCR System (Applied Biosystems).
2008-10-04 | E-GEOD-11306 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, psoriasis (chronic inflammation) study
2008-10-04 | GSE11307 | GEO
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. Keywords: Quantitative real time RT-PCR, cell type comparison
2008-10-04 | GSE11306 | GEO
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and inflammatory diseases, but it has been a challenge to evaluate theses processes quantitatively. Using two different microarray platforms, we first identified the comprehensive lineage specific transcriptomes of human lymphatic (LEC) and blood vascular (BVEC) endothelial cells. We identified 226 lymphatic signature genes and 342 signature genes for blood vascular endothelium. In silico analyses of the biologic pathways associated with these genes revealed lineage specific functions for each cell type. Using a selection of 85 identified lineage specific genes, we developed a TaqMan RT PCR based, microfluidic card formatted low density microvascular differentiation array (LD MDA) that can be used to reliably identify and quantify endothelial cells based on their lineage specific differentiation. Furthermore, using LD MDA, we were able to quantify levels of angiogenesis and lymphangiogenesis in tissue samples from patients with chronic inflammatory skin disease, indicating that this assay might be developed as a novel tool for the rapid and quantitative evaluation of pathological (lymph)angiogenesis in clinical and pre clinical studies. Keywords: cross-platform study
2011-04-01 | GSE6550 | GEO
Project description:Lymphangiogenesis plays a pivotal role in the pathogenesis of various vascular disorders, including ocular vascular diseases and cancers. Deregulation of N6-methyladenosine (m6A) modification has been identified as a key contributor to human diseases. However, the specific involvement of m6A modification in lymphatic remodeling remains poorly understood. In this study, we demonstrate that inflammatory stimulation and corneal sutures induce elevated levels of METTL3-mediated m6A modification. METTL3 knockdown inhibits lymphatic endothelial viability, proliferation, migration, and tube formation in vitro. METTL3 knockdown attenuates corneal sutures-induced lymphangiogenesis and intratumoral lymphangiogenesis initiated by subcutaneous grafts, consequently restraining corneal neovascularization, tumor growth, and tumor neovascularization in vivo. Mechanistically, METTL3 knockdown upregulates prostaglandin-endoperoxide synthase 2 (PTGS2) expression through an m6A-YTHDF2-dependent pathway, enhancing the synthesis of cyclopentenone prostaglandins (CyPGs). Aberrant CyPG production in lymphatic endothelial cells impairs mitochondrial oxidative phosphorylation, contributing to pathological lymphangiogenesis. Moreover, selective inhibition of METTL3 with STM2457 reduces m6A levels in lymphatic endothelial cells, effectively suppressing pathological lymphangiogenesis. This study provides compelling evidence that lymphatic-specific METTL3 plays a critical role in vascular patterning through prostaglandin metabolism reprogramming. Thus, METTL3 emerges as a promising target for treating pathological lymphangiogenesis.
2024-10-15 | GSE273930 | GEO
Project description:RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We used microarrays to link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to RhoB/VEZF1-mediated gene regulation in primary human blood versus lymphatic endothelial cells. Pure populations of human primary BVECs and LVECs silenced for RhoB or VEZF1 were used for RNA extraction and hybridization on Affymetrix microarrays. We extracted these cells from human male foreskins from at least four individuals and purified them using Dynabeads associated with vascular markers (CD31 and Podoplanin).
2013-10-28 | E-GEOD-51754 | biostudies-arrayexpress
Project description:Arianna Bianchi, Kevin J. Painter & Jonathan A. Sherratt. A mathematical model for lymphangiogenesis in normal and diabetic wounds. Journal of Theoretical Biology 383 (2015).
Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis) very few have been proposed for the regeneration of the lymphatic network. Moreover, lymphangiogenesis is markedly distinct from angiogenesis, occurring at different times and in a different manner. Here a model of five ordinary differential equations is presented to describe the formation of lymphatic capillaries following a skin wound. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from experimental and clinical data. The system is then solved numerically and the results are compared with the available biological literature. Finally, a parameter sensitivity analysis of the model is taken as a starting point for suggesting new therapeutic approaches targeting the enhancement of lymphangiogenesis in diabetic wounds. The work provides a deeper understanding of the phenomenon in question, clarifying the main factors involved. In particular, the balance between TGF-β and VEGF levels, rather than their absolute values, is identified as crucial to effective lymphangiogenesis. In addition, the results indicate lowering the macrophage-mediated activation of TGF-β and increasing the basal lymphatic endothelial cell growth rate, inter alia, as potential treatments. It is hoped the findings of this paper may be considered in the development of future experiments investigating novel lymphangiogenic therapies.
2024-09-02 | BIOMD0000000722 | BioModels