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Unknown,Transcriptomics,Genomics,Proteomics

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IL6 Related Cytokines Augment Angiogenesis in Nascent and Mature Human Endothelium Via JAK2 Signaling

ABSTRACT: While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis. 7 samples analyzed, 2 replicates for NRP1+CD34+, 3 replicates for NRP1+CD34-

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas Cimato

PROVIDER: E-GEOD-44328 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:While therapeutic angiogenesis holds promise for vascular diseases, progress has been limited due to discrepancies in defining adult endothelial progenitors. We have identified and characterized a population of pluripotent derived NRP1+CD34+ nascent endothelial cells, immediately diverged from NRP1+CD34- mesodermal cells. We contrasted the transcriptional profile of NRP1+ CD34+ nascent endothelial cells against undifferentiated human pluripotent stem cells and human umbilical vein endothelial cells (HUVECs) to gain insights into the pathways that are uniquely activated in formation of new endothelium. We found significant upregulation of IL-6 related growth factor receptors, including ciliary neurotrophic factor receptor (CNTFR), and their downstream JAK/STAT signaling components in NRP1+CD34+ endothelial cells. When exposed to CNTF, angiogenic sprouting of NRP1+CD34+ was induced in Matrigel, which was abolished with JAK2 inhibition. Furthermore, we found evidence of JAK2 dependent cytokine signaling in more mature endothelium, highlighting the significance of the IL6R/JAK2 pathway, well known in hematopoiesis, in vascular biology. The findings identify a novel group of growth factor receptors and downstream signaling components that may be targeted to modulate angiogenesis and vasculogenesis.

2013-12-14 | GSE44328 | GEO

Intermittent childhood hyperlipidaemia alters resident arterial macrophages and accelerates atherosclerosis

Project description:Peritoneal macrophages were obtained by intraperitoneal injection of cold PBS from Ldlr−/− mice reconstituted with Lyz2Cre+/− Nrp1flox/flox or Lyz2Cre+/− Nrp1+/+ bone marrow.

2024-07-30 | E-MTAB-12761 | biostudies-arrayexpress

Label-free quantitative proteome of AML CD34+ and mobilized PB CD34+ cells

Project description:The label-free quantitative proteome was generated for 42 primary AML patient samples enriched for CD34+ cells (or mononuclear cells in the case of NPMcyt sameples) and as controls 6 mobilized peripheral blood CD34+ cells were included. Furthermore, 6 AML cell lines were included, and also primary mesenchymal stem cells grown under normaoxia or hypoxia were included.

2022-03-15 | PXD030463 | Pride

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.

Project description:The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis. Four HUVEC donors were FACS-sorted by CD34 and divided in CD34-positive and CD34-negative fractions.

2012-01-05 | E-GEOD-34850 | biostudies-arrayexpress

Transcriptome Study of CD34+ hematopoietic progenitor from patients reached of Primary Myelofibrosis

Project description:An increased number of circulating CD34+ hematopoietic progenitors (HP) and a prominent amplification of dystrophic megakaryocytes (MK) are observed in PMF patients. As transcriptome data from CD34+ hematopoietic progenitors showed modulations of FLT3 and MAP kinase expression independently of the JAK2V617F mutation status Transcriptome analysis was performed on circulating CD34+ cells from PMF patients using Agilent 22K microarray and compared to CD34+ cells from blood and bone marrow from un-mobilized healthy donors. Indirect map: each tested sample was hybridzed with reference probe

2008-07-29 | E-GEOD-12234 | biostudies-arrayexpress

Comparison of WAT EPCs vs WAT ASCs

Project description:Human adipose tissue contains two populations of progenitors (EPCs and ASCs) with cooperative roles in breast cancer. EPCs (CD45-CD34+CD31+CD13-CCRL2+) can generate endothelial cells. ASCs (CD45-CD34+CD31-CD13+CD140b+) are mesenchymal progenitors which generated pericytes. CD13+ cells and CD13- cells from 7 Lipotransfer aspirate

2013-07-05 | E-GEOD-44302 | biostudies-arrayexpress

Expression data from CD34+/CD71- cells following knockdown of HSPA9

Project description:Knockdown of HSPA9 causes a dose-dependent decrease in erythroid maturation of CD34+ cells differentiated in culture. Due to differences in the degree of differentiation, a more homogeneous population was selected for using FACS and the gene expression profile of these cells was compared. We used a lentiviral vector (pLKO.1) expressing short hairpin RNAs targeting either luciferase (control shLUC) or HSPA9 (shHSPA9-433) to knock down expression of HSPA9. We isolated CD34+ cells from human cord blood (Day 0), transduced cells with a lentiviral vector (Day 1), selected for transduced cells with puromycin and differentiated them in erythroid culture media before FACS isolation of the CD34+/CD71- population (Day 5). Four independent CD34+ populations were isolated, differentiated and sorted for biologic replicates.

2016-02-23 | E-GEOD-78164 | biostudies-arrayexpress

RNAseq of HUVECs transfected with siRNA targeting Neuropilin 1 (NRP1) (si-NRP1) or a control non-targeting sequence (si-control) and exposed to unidirectional shear stress (20dyns/cm2), oscillatory flow (5dyn/cm2) or kept in absence of flow

Project description:HUVECs transfected with siRNA targeting Neuropilin 1(NRP1) (si-NRP1) or a control non-targeting sequence (si-control) and exposed to unidirectional shear stress (20dyns/cm2), oscillatory flow (5dyn/cm2) or kept in absence of flow.

2023-05-23 | E-MTAB-12191 | biostudies-arrayexpress

Regulatory T cells from colonic lamina propria [RNA-Seq]

Project description:The colonic lamina propria contains a distinct population of Foxp3+ T regulatory cells (Tregs) that modulate responses to commensal microbes. Analysis of gene expression revealed that the transcriptome of colonic Tregs is distinct from splenic and other tissue Tregs. Rorγ and Helios in colonic Tregs mark distinct populations: Rorγ+Helios- or Rorγ-Helios+ Tregs. We uncovered an unanticipated role for Rorγ, a transcription factor generally considered to be antagonistic to Foxp3. Rorγ in colonic Tregs accounts for a small but specific part of the colon-specific Treg signature. Nrp1- Tregs were sorted from Foxp3-cre.Rorcfl/fl mice, which have a Treg-selective deletion of Rorc, or paired WT littermates. For low-input RNAseq, 1,000 TCRb+CD4+YFP(Foxp3)+Nrp1- cells were double-sorted into Trizol, RNA extracted and reverse-transcribed using ArrayScript (Ambion). To reduce variability at least three replicates were generated.

2015-07-25 | E-GEOD-71304 | biostudies-arrayexpress

Normal counterpart in the identification of a molecular signature for leukemic promyelocytes

Project description:Gene expression profiles of 8 samples of CD34+derived normal promyelocytes We collected RNA from CD34+cells from healthy blood donors cultured in serum-free medium with G-CSF, IL-3 and GM-CSF

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