Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE206256 | GEO | 2022/09/20
REPOSITORIES: GEO
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Project description:We performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) utilising subcutaneous adipose tissue-derived stromal vascular fraction (SAT-SVF) as a negative control population. Baseline gene expression in ECFC fully corresponds to their endothelial specification and may contribute to the basement membrane organisation, fulfilling the requirements for the suitable cell population for in vitro pre-endothelialisation of tubular scaffolds.
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Project description:<p>The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer. </p>
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Project description:Endothelial colony forming cells (ECFC) are circulating endothelial progenitors that are recruited to sustain endothelial function, vascular growth and repair. They are particularly abundant in the perinatal period and can be isolated from umbilical cord blood, thus representing neonatal ECFC. In this study, we profiled neonatal ECFC depending on maternal metabolic derangements to investigate intrauterine epigenetic programming.
2023-07-21 | GSE228990 | GEO
Project description:Aims: Formation of a perfusable microvascular network (μVN) is critical for tissue engineering of solid organs. Stromal cells can support endothelial cell (EC) self-assembly into a μVN, but distinct stromal cell populations may play different roles in this process. Here we investigated the effects that two widely used stromal cells populations, fibroblasts (FBs) and pericytes (PCs), have on μVN formation. Methods and results: We examined the effects of adding defined stromal cell populations on the self-assembly of ECs derived from human endothelial colony forming cells (HECFCs) into perfusable μVNs in fibrin gels cast within a microfluidics chamber. ECs alone fail to fully assemble a perfusable μVN. Human lung FBs stimulate the formation of EC lined μVNs within microfluidic devices. RNA-seq analysis suggested that FBs produce high levels of hepatocyte growth factor (HGF), and addition of recombinant HGF improved μVN formation within devices. Human placental PCs could not substitute for FBs, but in the presence of FBs, PCs closely associated with ECs, formed a common basement membrane, extend microfilaments intercellularly, and reduced microvessel diameters. Conclusions: Different stromal cell types provide different functions in microvessel assembly by ECs. FBs support μVN formation by providing paracrine growth factors whereas PCs directly interact with ECs to modify microvascular morphology.
2019-12-31 | GSE122389 | GEO
Project description:Human induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells differentiate into cells of the endothelial lineage, but derivation of cells with human umbilical cord blood endothelial colony forming cell (ECFC)-like properties has not been reported. Here we describe a novel serum- and stromal cell-free ECFC differentiation protocol for the derivation of clinically relevant numbers of ECFCs (> 108) from hiPS and hES cells. We identified NRP-1+CD31+ selected cells that displayed a stable endothelial phenotype exhibiting high clonal proliferative potential, extensive replicative capacity, formation of human vessels that inosculated with host vasculature upon transplantation, but lacking in teratoma formation in vivo. We also identified NRP-1-VEGF165-KDR-mediated activation of KDR as a critical mechanism for the emergence and derivation of ECFCs from hiPS and hES cells. This protocol advances the field by generating highly replicative but stable endothelial cells for use as a potential cell therapy for human clinical disorders. Transcriptome sequencing of undifferentiated day 0 hiPS cells, Day 3 differentiated hiPS-derived mesoderm proginator cells, Day 12 hiPS-derived NRP-1+CD31+ cells, Day 12 H9-hES-derived NRP-1+CD31+ cells and cord blood-derived Endothelial colony forming cells.
2014-07-18 | E-GEOD-49074 | biostudies-arrayexpress
Project description:Endothelial cells (ECs) are by definition plastic and multipotent. EC plasticity was evaluated by stimulating EC to physiological and pathological stress coupled with antiproliferative therapies.
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Project description:The transport of gases, nutrients, metabolites and cells - a prerequisite for proper organogenesis and tissue homeostasis - requires a functional circulatory system consisting of arteries and veins, separated by intervening capillary networks. Despite their shared origin and some common functions, endothelial cells (ECs), which line every blood vessel, display profound structural and functional heterogeneity unique to the organ and tissue that they reside in. The diversity of phenotypes that ECs can adopt suggest substantial plasticity and indicates that heterogeneity is a core endothelial property that allows ECs to fulfill their multiple tasks. While the anatomical heterogeneity of blood vessels across different organs has been appreciated for centuries, the molecular basis of the variation within the vertebrate vascular tree is poorly understood. To decipher the transcriptional and epigenetic basis of endothelial heterogeneity across organs, and to determine how ECs mature during development, we surveyed the transcriptional and accessible chromatin landscape of ECs from the brain, retina, heart, liver, lung, and kidney of E12.5, P6, and adult mice. Through analysis of differential gene expression signatures, as well as chromatin accessibility, we have identified unique transcripts, as well as regulatory regions, that define each organ bed and developmental time point. Additionally, through single cell RNA-seq profiling of the embryonic and adult mouse we have determined that the endothelium of a single organ - in this case the brain - uses a diverse set of gene regulatory networks to mature and create a functional blood brain barrier.
2022-07-01 | GSE185345 | GEO
Project description:The identification of circulating endothelial progenitor cells has led to speculation regarding their origin as well as their contribution to neovascular development. Two distinct types of endothelium make up the blood and lymphatic vessel system. However, it has yet to be determined whether there are distinct lymphatic-specific circulating endothelial progenitor cells. We isolated circulating endothelial colony forming cells (ECFCs) from whole peripheral blood. These cells are endothelial in nature, as defined by their expression of endothelial markers and their ability to undergo capillary morphogenesis in three-dimensional culture. A subset of isolated colonies express markers of lymphatic endothelium, including VEGFR-3 and Prox-1, with low levels of VEGFR-1, a blood endothelial marker, while the bulk of the isolated cells express high VEGFR-1 levels with low VEGFR-3 and Prox-1 expression. The different isolates have differential responses to VEGF-C, a lymphatic endothelial specific cytokine, strongly suggesting that there are lymphatic specific and blood specific ECFCs. Global analysis of gene expression revealed key differences in the regulation of pathways involved in cellular differentiation between blood and lymphatic-specific ECFCs. These data indicate that there are two distinguishable circulating ECFC types, blood and lymphatic, which are likely to have discrete functions during neovascularization. RNA was isolated from 2 blood-specific ECFC cell lines and 2 lymphatic-specific ECFC cell lines 3 separate times each
2014-06-23 | E-GEOD-54416 | biostudies-arrayexpress
Project description:While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)-derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell-derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient-specific models.
| S-EPMC6402823 | biostudies-literature
Project description:Human induced pluripotent stem (hiPS) cells and human embryonic stem (hES) cells differentiate into cells of the endothelial lineage, but derivation of cells with human umbilical cord blood endothelial colony forming cell (ECFC)-like properties has not been reported. Here we describe a novel serum- and stromal cell-free ECFC differentiation protocol for the derivation of clinically relevant numbers of ECFCs (> 108) from hiPS and hES cells. We identified NRP-1+CD31+ selected cells that displayed a stable endothelial phenotype exhibiting high clonal proliferative potential, extensive replicative capacity, formation of human vessels that inosculated with host vasculature upon transplantation, but lacking in teratoma formation in vivo. We also identified NRP-1-VEGF165-KDR-mediated activation of KDR as a critical mechanism for the emergence and derivation of ECFCs from hiPS and hES cells. This protocol advances the field by generating highly replicative but stable endothelial cells for use as a potential cell therapy for human clinical disorders.
2014-07-18 | GSE49074 | GEO