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Expression analysis of mouse retinas after treatment with VEGF-A or Dll4-Fc.

ABSTRACT: Transcriptional profiling of retinas extracted from mouse pups 24 hours after IVT injection (at P8) of 1 microgram VEGFA, 4 micrograms Dll4-Fc, or 4 microgram hFc alone. Goal was to determine the mechanism by which inhibiting Dll4/Notch pathway is vasoprotective during retinal development.

ORGANISM(S): Mus musculus

PROVIDER: GSE28516 | GEO | 2011/04/13

SECONDARY ACCESSION(S): PRJNA138971

REPOSITORIES: GEO

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Expression analysis of mouse retinas after treatment with VEGF-A or Dll4-Fc.

Project description:Transcriptional profiling of retinas extracted from mouse pups 24 hours after IVT injection (at P8) of 1 microgram VEGFA, 4 micrograms Dll4-Fc, or 4 microgram hFc alone. Goal was to determine the mechanism by which inhibiting Dll4/Notch pathway is vasoprotective during retinal development. Three-condition experiment: VEGF-A treated vs hFc, Dll4-Fc vs hFc. Four replicates each for Dll4-Fc and hFc, five for VEGF-A.

2011-04-13 | E-GEOD-28516 | biostudies-arrayexpress

Gene expression profile of DLL4+ and DLL4- Hemato-Endothelial Progenitors (HEPs) subpopulations

2014-05-01 | GSE56881 | GEO

Gene expression profile of DLL4+ and DLL4- Hemato-Endothelial Progenitors (HEPs) subpopulations

Project description:In hESCs, expression of the Notch ligand DLL4 parallels the emergence of bipotent hematoendothelial progenitors (HEPs) and promotes their hematopoietic differentiation. During differentiation, DLL4 is only expressed in a subpopulation of HEPs. To study the developmental fate of the two subpopulations of HEPs identified by DLL4 expression, we FACS-isolated DLL4high and DLL4low/- HEPs at day 15 of differentiation and performed gene expression analysis using microarrays 10^5 DLL4high and DLL4low/- HEPs purified by FACS from H9 and AND1 hEBs at day 15 of hematopoietic differentiation were used for gene expression analysis using Whole Human Genome Oligo Microarray chips (Agilent Technologies).

2014-05-01 | E-GEOD-56881 | biostudies-arrayexpress

Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment

Project description:Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment C57BL/6 mice were injected with anti-DLL4, or an isotype control antibody as controls. Two weeks later mice were sacrificed, and thymi was harvested from 4 anti-DLL4 and 4 control animals. Total thymocytes, DN cells (CD4-CD8-) and DN1(CD4-CD8- CD44+CD25-) cells were isolated. Samples included in this data set are: 3 Thymocytes-anti-DLL4; 3 Thymocytes-isotype control; 3 DN1-anti-DLL4; 2 DN1-isotype controls; 3 DN-anti-DLL4; 3 DN-isotyoe control.

2012-04-29 | E-GEOD-24296 | biostudies-arrayexpress

Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade

Project description:Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase MFng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade.

2019-12-03 | GSE110614 | GEO

RNAseq of wild type (WT) and Dll4+/- mouse lung

Project description:We report the application of RNA sequencing for high-throughput profiling of gene epxression in WT and Dll4 +/- lung

2021-01-14 | GSE164732 | GEO

Dll4 inhibition promotes angiogenesis and graft volume retention in cell-assisted lipotransfer

Project description:Purpose: Autologous fat grafting is one of the most effective and safest treatment for soft tissue restoration and augmentation, and many efforts has been done to improve its efficiency including adipose tissue derived stem cell (ASC) supplementation. Here, we evaluated the role of Notch ligand Delta-like ligand 4 (Dll4) in angiogenesis in grafted fat and the effect on graft survival using the murine fat graft model, and its impact on the ASC supplementation. Methods: We performed RNA-seq analysis of 3 mouse fat graft groups: 1) control fat grafts, 2) ASC added fat graft, and 3) ASC added fat graft with Dll4 inhibition. The fat grafts were harvested 8 weeks after grafting (n=4), and generated mRNA profiles by deep sequencing using Illumina NovaSeq 6000. Results: We found that when we treated Dll4 blocking antibody to inhibit Dll4, which was highly expressed in endothelial cells (ECs) of grafted fat, angiogenesis in the grafted fat was significantly induced, promoting fat graft retention. In addition, this effect was shown to synergistically improve the fat graft retention when ASCs were concomitantly supplemented. Transcriptome analysis further identified that the expression of the junctional proteins was increased in the ECs and inflammatory processes were downregulated in the grafted fat with ASC supplementation and Dll4 inhibition. Conclusions: This study serves as a basis for developing new potential therapeutic approaches to improve graft retention after cell-assisted transfer by Dll4 inhibition.

2023-12-05 | GSE190243 | GEO

Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment

Project description:Molecular mechanism underline immune cell type population shift upon anti-DLL4 treatment

2012-04-30 | GSE24296 | GEO

Transcription profiling by array of mouse P6 retinal endothelial cells extracted from wildtype and dll4 heterozygous mice

Project description:Transcription profiling of P6 retinal endothelial cells (ECs) extracted from retinas wild_type and dll4 heterozygous mice

2011-01-10 | E-MTAB-347 | biostudies-arrayexpress

Notch ligand Dll4 impairs the recruitment of hemogenic cells into intra-aortic clusters and limits hematopoietic stem cell production.

Project description:Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium in the embryonic aorta. In most vertebrates, hemogenic cells protrude into the aortic lumen forming clusters where the hematopoietic features are acquired. Although much is known about the molecular characteristics of the hematopoietic cells, we still lack basic understanding on the origin and 3D-organization of intraortic hematopoietic clusters (IAHC) in the mouse embryo and how they evolve over time. Here we use advanced live imaging techniques of organotypic slice cultures, clonal analysis, and mathematical modelling to show that IAHC formation is a two-step process. First, a hemogenic progenitor buds up from the endothelium and undergoes division forming the monoclonal core of the cluster. Next, cells from the surrounding hemogenic endothelium are recruited into the IAHCs, increasing their size and heterogeneity. We found that the recruitment phase of IAHC formation is negatively regulated by Notch signalling via the Delta-like-4 (Dll4) Notch ligand. We show that blocking of Dll4 promotes the entrance of new hemogenic Gfi1+ cells into the IAHC and increases the number of cells that acquire HSC activity. Mathematical modelling based on our data provides estimation of the cluster lifetime and the average recruitment time of hemogenic cells to the cluster under physiologic and Dll4-inhibited conditions. Single cell transcriptomic analysis indicates that cell identities are preserved after Dll4 blockage. Our data provides for the first time a detailed characterization of the aortic hematopoietic stem cell niche and its maturation dynamics, identifying the Notch ligand Dll4 as a major molecular player governing dynamics of cluster formation and HSCs production.

2020-01-10 | GSE124875 | GEO

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