Dll4 inhibition promotes angiogenesis and graft volume retention in cell-assisted lipotransfer
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ABSTRACT:
PROVIDER: PRJNA786534 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17139580_1.fastq.gz | Fastqsanger.gz | |||
| SRR17139580_2.fastq.gz | Fastqsanger.gz | |||
| SRR17139581_1.fastq.gz | Fastqsanger.gz | |||
| SRR17139581_2.fastq.gz | Fastqsanger.gz | |||
| SRR17139582_1.fastq.gz | Fastqsanger.gz |
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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
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
2014-05-01 | GSE56881 | GEO
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
Project description:We report the histone retention loci alteration in human sperm cell genome after density selection comparison the histone binding site alteration with high-throughput sequencing technique.
2016-08-01 | E-GEOD-71483 | biostudies-arrayexpress
Project description:Background: Autologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival. Methods: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells. Results: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors. Conclusions: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.
2023-05-08 | GSE231511 | GEO
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
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
Project description:Notch signaling promotes T-cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like ligand DLL4. To assess if Notch’s effects are evolutionarily conserved and identify key mechanisms, we studied antibody-mediated DLL4 blockade in a non-human primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved post-transplant survival with striking, durable protection from gastrointestinal GVHD, out of proportion to other disease sites. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T-cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4β7 in conventional T-cells while preserving α4β7 in regulatory T-cells, with findings suggesting increased 1 competition for 4 binding in conventional T-cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4β7 integrin in T-cells after allo-HCT. Altogether, DLL4/Notch blockade decreased effector T-cell infiltration into the gut, with increased regulatory to conventional T-cell ratios early after allo-HCT. Our results identify a conserved, biologically unique and targetable role of DLL4/Notch signaling in GVHD.
2023-07-14 | GSE228838 | GEO
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
Project description:Background: The mechanisms underlying fat graft survival are poorly understood. Here, we performed unbiased transcriptomics analysis of mouse fat graft model to find out the molecular mechanism of free fat graft survival. Methods: We conducted RNA-sequencing (RNA-seq) analysis of mouse free subcutaneous fat graft model at day 3 and 7 following grafting (n=5). High-throughput sequencing was performed as paired-end using NovaSeq6000 (Illumina, CA, USA). The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heat map generation, and Gene set enrichment analysis. Results: PCA and heat map data revealed global differences in the transcriptome of grafted fat when compared with non-graft control. The top meaningful up-regulated gene sets in the grafted fat were related to epithelial mesenchymal transition and hypoxia by day 3, and angiogenesis by day 7. Mechanistically, the glycolysis pathway was commonly upregulated in the grafted fat at day 3 (FDR q=0.012) and day 7 (FDR q=0.084). In subsequent experiments, pharmacological inhibition of glycolytic pathway in the grafted fat with 2-Deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n=5). Conclusions: Global transcriptome analysis and pharmacologic inhibition study revealed that free adipose tissue grafts undergo metabolic reprogramming towards glycolytic pathway. Whether targeting the pathway wound enhance graft survival rate remains to be investigated.
2024-06-01 | GSE203599 | GEO