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Genetic module and miRNome trait analyses reflect the distinct biological features of endothelial progenitor cells from different anatomic locations

ABSTRACT: Background: Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair, yet EPCs from different anatomic locations possess unique biological properties. The underlying mechanisms are unclear. Method: We performed transcriptome analysis for EPCs isolated from 2 different sources: cord blood (CB) or adult peripheral blood (PB). Both gene expression microarray and small RNA sequencing (smRNA-seq) technologies were applied. Results: EPCs from CB expressed abundant genes involved in cell cycle, hypoxia signalling and blood vessel development, correlating with the phenotypes that CB-EPCs proliferated more rapidly, migrated faster, and formed tubule structure more efficiently. smRNA-seq further deciphered miRNome patterns in EPCs isolated from CB or PB: 54 miRNAs were enriched in CB-EPCs, while another 50 in PB-EPCs. Specifically, CB-EPCs expressed more angiogenic miRNAs such as miR-31, while PB-EPCs possessed more tumor suppressive miRNAs including miR-10a. Knocking down miR-31 levels in CB-EPCs suppressed cell migration and microtubule formation, while overexpressing miR-31 in PB-EPCs helped to recapitulate some of CB-EPC functions. Conclusion: Our results show the foundation for a more detailed understanding of EPCs from different anatomic sources. Stimulating the expression of angiogenic microRNAs or genes in EPCs of low activity (such as those from patients with cardiovascular diseases) might allow the development of novel therapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39763 | GEO | 2012/09/21

SECONDARY ACCESSION(S): PRJNA171608

REPOSITORIES: GEO

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Genetic module and miRNome trait analyses reflect the distinct biological features of endothelial progenitor cells from different anatomic locations

Project description:Background: Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair, yet EPCs from different anatomic locations possess unique biological properties. The underlying mechanisms are unclear. Method: We performed transcriptome analysis for EPCs isolated from 2 different sources: cord blood (CB) or adult peripheral blood (PB). Both gene expression microarray and small RNA sequencing (smRNA-seq) technologies were applied. Results: EPCs from CB expressed abundant genes involved in cell cycle, hypoxia signalling and blood vessel development, correlating with the phenotypes that CB-EPCs proliferated more rapidly, migrated faster, and formed tubule structure more efficiently. smRNA-seq further deciphered miRNome patterns in EPCs isolated from CB or PB: 54 miRNAs were enriched in CB-EPCs, while another 50 in PB-EPCs. Specifically, CB-EPCs expressed more angiogenic miRNAs such as miR-31, while PB-EPCs possessed more tumor suppressive miRNAs including miR-10a. Knocking down miR-31 levels in CB-EPCs suppressed cell migration and microtubule formation, while overexpressing miR-31 in PB-EPCs helped to recapitulate some of CB-EPC functions. Conclusion: Our results show the foundation for a more detailed understanding of EPCs from different anatomic sources. Stimulating the expression of angiogenic microRNAs or genes in EPCs of low activity (such as those from patients with cardiovascular diseases) might allow the development of novel therapeutic strategies. EPC from cord blood or peripheral blood that outgrown after 2-4 week culture were collected. The RNA are extracted and profiled by Affymetrix GeneChip U133 plus 2.0 expression array. This submission represents gene expression microarray component of study.

2012-09-21 | E-GEOD-39763 | biostudies-arrayexpress

Transcriptome Analysis of miRNAs in Umbilical cord blood exosomes of Intrauterine Growth Restriction Pigs

Project description:Dysfunctional umbilical cord blood (CB) is an important factor for the development of IUGR in utero. However, the genetic mechanism underlying the miRNAs in CB exosomes influence the development of IUGR is not well characterized. Herein, we present a comprehensive investigation of miRNA transcriptome of umbilical cord vein and artery between IUGR and normal littermate. We total identified 636 unique miRNAs. There were 116 significant differentially expressed (DE) miRNAs between umbilical vein of normal (NV) and IUGR (IV) and 226 DE miRNAs between umbilical artery of normal (NA) and IUGR (IA) (P < 0.001). Cluster analysis revealed that umbilical artery had the most striking divergence, implied it plays more prominent role in the development of IUGR. The miRNAs enriched in NA mainly participate in blood vessel development, regulation of transcription and growth. The miRNAs highly expressed in IA mainly enriched in apoptosis, cell death, embryonic development and immune system development Besides, miRNAs related to oxygen transfer (miR-210, miR-424), angiogenesis (miR-130a, miR-150, miR-34a) and immune system development (miR-181a, miR-155) were lower expressed in IUGR. Our findings demonstrate that CB derived miRNAs participate in fetal epigenetic regulation during pregnancy, which may supply a new explanation for abnormal embryologic development and some congenital diseases.

2018-12-26 | GSE87111 | GEO

Functional Analysis and Gene Expression Profile of Umbilical Cord Blood Regulatory T Cells

Project description:Since the role of cord blood (CB) regulatory T cells (Tregs) for the suppression of the allogeneic T-cell response is under investigation, we analyzed and compared the functional properties and gene expression profile of Tregs expanded from CB units or from the peripheral blood (PB) of helathy donors. Tregs were purified from 23 CB units and from the PB of 13 donors and expanded for 6 days with anti-CD3, anti-CD28 and IL-2. Immunophenotypic analyses were performed, and suppressor activity of expanded Tregs was measured in mixed lymphocyte reaction (MLR) cultures. The IL-10 production capacity was tested and gene expression profile experiments were performed on 6 Tregs from PB and 4 from CB. CB and PB Tregs had similar immunophenotypic features. Tregs from CB presented a higher expansion capacity and genomic characterization showed in CB-derived Tregs a significant enrichments of genes involved in cell proliferation, chromatin modification and regulation of gene expression in CB-derived Tregs. All samples were positive for the Foxp3 gene and protein after expansion. CB and PB expanded Tregs exerted a comparable and potent suppressive function of MLR and presented a high in vitro IL-10 production capacity. Gene profile analysis also revealed for PB Tregs a significant enrichments of genes involved in the adaptive immune response.

2010-12-31 | GSE22501 | GEO

High-resolution profiling and analysis of viral and host small RNAs during human cytomegalovirus infection

Project description:Small RNA deep sequencing analysis was conducted on primary human fibroblasts infected with human cytomegalovirus (HCMV). HCMV-encoded miRNAs accumulated to ~20% of the total smRNA population at late stages of infection, and our analysis led to improvements in viral miRNA annotations and identification of novel HCMV miRNAs. Through crosslinking and immunoprecipitation of Argonaute-bound RNAs from infected cells, followed by high-throughput sequencing (Ago CLIP-seq), we obtained direct evidence for incorporation of all HCMV miRNAs into the endogenous host silencing machinery. Additionally, significant upregulation was observed during infection for a host miRNA cluster containing miR-96, miR-182 and miR-183. We also identified novel non-miRNA forms of virus-derived smRNAs, revealing greater complexity within the smRNA population during HCMV infection.

2011-11-10 | GSE33584 | GEO

Functional Analysis and Gene Expression Profile of Umbilical Cord Blood Regulatory T Cells

2010-12-31 | E-GEOD-22501 | biostudies-arrayexpress

A global transcriptome analysis of keratinocytes upon suppression of endogenous microRNA-31

Project description:MiR-31 is one of the most highly overexpressed miRNAs in psoriasis skin; however, its biological role in the disease has not been studied. Here we show that miR-31 is markedly overexpressed in psoriasis keratinocytes. To study the biological role of miR-31 in keratinocytes, we transfected miR-31 hairpin inhibitor (anti-miR-31) into primary human keratinocytes to inhibit endogenous miR-31. We performed a global transcriptome analysis of keratinocytes upon suppression of endogenous miR-31 using Affymetrix arrays.

2012-10-30 | GSE41905 | GEO

Whole-transcriptome profiling of neovascularized corneas reveal miR-204 as a potent biotherapy deliverable by rAAVs [RNA-Seq]

Project description:Current drugs that directly target pro-angiogenic factors to inhibit or reverse corneal neovascularization, the major sight-threatening pathology caused by angiogenic stimuli, require multiple rounds of administration and have limited efficacies. Here we report the profiling of anti-angiogenic corneal microRNAs (miRNAs), and a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs). By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali-burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs. Among these corneal miRNAs, we selected miR-204 and assessed its efficacy as a therapeutic miRNA in injured corneas. Our results show that delivery of miR-204 by rAAV is efficacious and safe for mitigating corneal NV. Overall, our work demonstrates the discovery of therapeutic miRNAs in corneal disorders and their translation into viable clinical vectors.

2018-10-26 | GSE89537 | GEO

Whole-transcriptome profiling of neovascularized corneas reveal miR-204 as a potent biotherapy deliverable by rAAVs [nCounter - microRNAs]

2018-10-26 | GSE89536 | GEO

High-resolution profiling and analysis of viral and host small RNAs during human cytomegalovirus infection

2011-11-10 | E-GEOD-33584 | biostudies-arrayexpress

Hsa-miR-31-5p controls a metabolic switch in psoriatic keratinocytes that identifies therapeutic intervention

Project description:Next to genetic alterations, it is being recognized that the cellular environment also acts as a major determinant in onset and progression of disease. In cases where different cell types contribute to the final disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. A number of skin diseases, including psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Activation of immune cells involves increased glucose consumption thereby intrinsicly limiting glucose availability for other cell types. Thus, these type of skin diseases require metabolic adaptations that enable coexistence between hyperproliferative keratinocytes and activated immune cells in a nutrient-limited environment. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes within the psoriatic skin. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and enables increased survival of keratinocytes under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also secretion of immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

2023-02-06 | PXD029030 | Pride

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