Comparative Transcriptomics of Ex Vivo, Patient-Derived Endothelial Cells Reveals Novel Pathways Associated With Type 2 Diabetes Mellitus

Beckman, Joshua A.; Doherty, Sean; Feldman, Zachary B.; Banks, Emily S.; Moslehi, Javid; Jaffe, Iris Z.; Hamburg, Naomi M.; Sheng, Quanhu; Brown, J.

doi:10.1016/j.jacbts.2019.05.012

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…This is a surprising result, considering earlier findings of morphological differences between normoglycemic and diabetic subjects in both human and rodent studies. Previous work using RNA-Seq has identified differences in the expression of several genes in cubital vein endothelial cells derived from non-diabetic patients and patients with type 2 diabetes 27 . However, the study by Beckman et al involved macrovascular endothelial cells, which are not directly comparable to MVEC.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism

Jonsson

Hedin

Müller

et al. 2020

Sci Rep

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In experimental studies, pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects. Even so, almost no information is available concerning human islet microvascular endothelial cell (MVEC) physiology and gene expression. In this study, islets and exocrine pancreatic tissue were acquired from organ donors with normoglycemia or impaired glucose metabolism (IGM) immediately after islet isolation. Following single-cell dissociation, primary islet- and exocrine MVECs were obtained through fluorescence-activated cell sorting (FACS) and transcriptional profiles were generated using AmpliSeq. Multiple gene sets involved in general vascular development and extracellular matrix remodeling were enriched in islet MVEC. In exocrine MVEC samples, multiple enriched gene sets that relate to biosynthesis and biomolecule catabolism were found. No statistically significant enrichment was found in gene sets related to autophagy or endoplasmic reticulum (ER) stress. Although ample differences were found between islet- and exocrine tissue endothelial cells, no differences could be observed between normoglycemic donors and donors with IGM at gene or gene set level. Our data is consistent with active angiogenesis and vascular remodeling in human islets and support the notion of ongoing endocrine pancreas tissue repair and regeneration even in the adult human.

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Section: Discussionmentioning

confidence: 99%

Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism

Jonsson

Hedin

Müller

et al. 2020

Sci Rep

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“…Endothelial cells from cubital vein RNA-Seq -5 T2D, 5 HC [36] Whole blood RNA-Seq -6 T2D with thirst and fatigue, 6 HC [37] Neutrophils RNA-Seq qPCR 5 newly diagnosed T2D, 5 HC [38] Visceral adipose tissue RNA-Seq qPCR 10 T2D, 10 HC [39] Adipose tissue from thigh RNA-Seq qPCR 5 T2D, 5 HC [40] Neutrophils RNA-Seq -11 T2D, 7 HC [41] Human islet cells Single-cell RNA-Seq RNA in situ hybridization 4 T2D, 6 HC [42] Human islet cells Single-cell RNA-Seq -6 T2D, 12 HC [43] Human islet cells Single-cell RNA-Seq -1 T1D donor, 3 T2D donors, 2 children, 3 HC [44] Human islet cells Single-cell RNA-Seq RNA in situ hybridization 3 T2D, 5 HC [45] PBMC-peripheral blood mononuclear cells; HC-healthy controls; T1D-type 1 diabetes; T2D-type 2 diabetes mellitus; GDM-gestational diabetes mellitus; CAD-coronary artery disease. Studies are divided by method (microarray, RNA-seq, single-cell RNA-Seq).…”

Section: Sample Type Transcriptomic Technique Validation Study Group ...mentioning

confidence: 99%

“…The endothelial dysfunction, inevitably leading to atherosclerosis, CAD, and microvascular complications, is known to often accompany T2D [ 77 ]. The comparative analysis of gene expression in the endothelial cells of T2D individuals and healthy controls revealed 51 upregulated and 101 downregulated DEGs associated with metabolism and growth pathways [ 36 ]. It is evident that the analysis of endothelial cells is not possible in routine practice to identify risk groups for cardiovascular complications in T2D patients.…”

Section: Transcriptome Studies In T2dmentioning

confidence: 99%

Overview of Transcriptomic Research on Type 2 Diabetes: Challenges and Perspectives

Tonyan

Nasykhova

Danilova

et al. 2022

Genes

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Type 2 diabetes (T2D) is a common chronic disease whose etiology is known to have a strong genetic component. Standard genetic approaches, although allowing for the detection of a number of gene variants associated with the disease as well as differentially expressed genes, cannot fully explain the hereditary factor in T2D. The explosive growth in the genomic sequencing technologies over the last decades provided an exceptional impetus for transcriptomic studies and new approaches to gene expression measurement, such as RNA-sequencing (RNA-seq) and single-cell technologies. The transcriptomic analysis has the potential to find new biomarkers to identify risk groups for developing T2D and its microvascular and macrovascular complications, which will significantly affect the strategies for early diagnosis, treatment, and preventing the development of complications. In this article, we focused on transcriptomic studies conducted using expression arrays, RNA-seq, and single-cell sequencing to highlight recent findings related to T2D and challenges associated with transcriptome experiments.

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“…Further examination with culture of normal HAECs showed that Wnt5a protein activated JNK and abrogated the insulin stimulated eNOS activation [ 111 ]. More recently, using low-input RNA sequencing, Beckman et al performed comparative gene expression profiling of venous ECs and identified 51 significantly upregulated and 101 significantly downregulated genes in T2DM ECs compared with control ECs [ 112 ]. Bioinformatics analysis revealed that the mitochondrial metabolic and androgen signaling pathways were impaired, while TGF- β and Cyclin-D1 signaling pathways were activated in T2DM ECs [ 112 ].…”

Section: Study Of Ecfcs To Help Decipher Disease Pathogenesismentioning

confidence: 99%

“…More recently, using low-input RNA sequencing, Beckman et al performed comparative gene expression profiling of venous ECs and identified 51 significantly upregulated and 101 significantly downregulated genes in T2DM ECs compared with control ECs [ 112 ]. Bioinformatics analysis revealed that the mitochondrial metabolic and androgen signaling pathways were impaired, while TGF- β and Cyclin-D1 signaling pathways were activated in T2DM ECs [ 112 ]. However, the detailed mechanisms of how these altered pathways contribute to endothelial dysfunction remain to be clarified.…”

Section: Study Of Ecfcs To Help Decipher Disease Pathogenesismentioning

confidence: 99%

Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review

Zhang

Cannavicci

Kutryk

2022

Stem Cells International

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Endothelial cell (EC) dysfunction has been implicated in a variety of pathological conditions. The collection of ECs from patients is typically conducted postmortem or through invasive procedures, such as surgery and interventional procedures, hampering efforts to clarify the role of ECs in disease onset and progression. In contrast, endothelial colony-forming cells (ECFCs), also termed late endothelial progenitor cells, late outgrowth endothelial cells, blood outgrowth endothelial cells, or endothelial outgrowth cells, are obtained in a minimally invasive manner, namely, by the culture of human peripheral blood mononuclear cells in endothelial growth medium. ECFCs resemble mature ECs phenotypically, genetically, and functionally, making them excellent surrogates for ECs. Numerous studies have been performed that examined ECFC function in conditions such as coronary artery disease, diabetes mellitus, hereditary hemorrhagic telangiectasia, congenital bicuspid aortic valve disease, pulmonary arterial hypertension, venous thromboembolic disease, and von Willebrand disease. Here, we provide an updated review of studies using ECFCs that were performed to better understand the pathophysiology of disease. We also discuss the potential of ECFCs as disease biomarkers and the standardized methods to culture, quantify, and evaluate ECFCs and suggest the future direction of research in this field.

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Comparative Transcriptomics of Ex Vivo, Patient-Derived Endothelial Cells Reveals Novel Pathways Associated With Type 2 Diabetes Mellitus

Abstract: Visual Abstract

Cited by 12 publications

References 31 publications

Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism

Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism

Overview of Transcriptomic Research on Type 2 Diabetes: Challenges and Perspectives

Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review

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