Minna U. Kaikkonen
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View article: Single-cell to pre-clinical evaluation of <i>Trem2</i> , <i>Folr2</i> , and <i>Slc7a7</i> as macrophage-associated biomarkers for atherosclerosis
Single-cell to pre-clinical evaluation of <i>Trem2</i> , <i>Folr2</i> , and <i>Slc7a7</i> as macrophage-associated biomarkers for atherosclerosis Open
Aims Atherosclerosis is a major global health challenge, with limited diagnostic and therapeutic options. Macrophages drive disease progression, but their tissue-specific phenotypes and functions remain poorly defined. This study aims to e…
View article: MicroRNA gene dynamics in immune cell subpopulations during aging and atherosclerosis disease development at single-cell resolution
MicroRNA gene dynamics in immune cell subpopulations during aging and atherosclerosis disease development at single-cell resolution Open
View article: Slc7a7 licenses macrophage glutaminolysis for restorative functions in atherosclerosis
Slc7a7 licenses macrophage glutaminolysis for restorative functions in atherosclerosis Open
Atherosclerosis is a life-threatening condition characterized by chronic inflammation of the arterial wall. Atherosclerotic plaque macrophages are key players at the site of disease, where metabolic reprogramming dictates the progression o…
View article: Adipose tissue-derived fibroblasts engage in immune-stromal crosstalk during obesity-aggravated atherosclerosis in mice
Adipose tissue-derived fibroblasts engage in immune-stromal crosstalk during obesity-aggravated atherosclerosis in mice Open
Background Atherosclerosis is a common disorder where changes in vascular wall and in the surrounding perivascular adipose tissue are evident. However, how multiple cell types contribute to the disease at the cellular level remains poorly …
View article: Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk
Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk Open
To systematically identify causal genetic mechanisms that confer risk for coronary artery disease (CAD) in GWAS loci, we mapped genome-wide variant-to-enhancer-to-gene (V2E2G) links in vascular smooth muscle cells (SMC). Enhancers identifi…
View article: Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis
Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis Open
Macrophage-to-foam cell transition is an integral part of atherosclerotic plaque progression. Particularly, oxidized low-density lipoprotein (oxLDL) is a driving factor in foam cell formation, altering macrophage function and metabolism. T…
View article: Integrated ambient modeling and genetic demultiplexing of single-cell RNA+ATAC multiome experiments with Ambimux
Integrated ambient modeling and genetic demultiplexing of single-cell RNA+ATAC multiome experiments with Ambimux Open
Single cell technologies have advanced at a rapid pace, providing assays for various molecular phenotypes. Droplet-based single cell technologies, particularly those based on nuclei isolation, such as simultaneous RNA+ATAC single-cell mult…
View article: Alzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial
Alzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial Open
Alzheimer's disease and coronary artery disease are common late-life chronic conditions and share multiple risk factors, including Apolipoprotein E (APOE) ε4 allele. A meta-analysis of two multidomain lifestyle intervention trials indicate…
View article: Genome-wide Cross-multi-trait Analysis into Shared Genetic Architecture of Coronary Artery Disease and Aortic Aneurysms
Genome-wide Cross-multi-trait Analysis into Shared Genetic Architecture of Coronary Artery Disease and Aortic Aneurysms Open
While affecting distinct vascular territories, coronary artery disease, abdominal aortic aneurysms and thoracic aortic aneurysms share similar risk factors and pathophysiological resemblance. To identify novel pleiotropic and heterogenous …
View article: Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques
Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques Open
View article: Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis
Epigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis Open
View article: Nucleus softens during herpesvirus infection
Nucleus softens during herpesvirus infection Open
Nuclear mechanics is remodeled not only by extracellular forces but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the nuclear structures undergo drastic reorganizat…
View article: Integration of single cell omics with biobank data discovers<i>trans</i>effects of<i>SREBF1</i>abdominal obesity risk variants on adipocyte expression of more than 100 genes
Integration of single cell omics with biobank data discovers<i>trans</i>effects of<i>SREBF1</i>abdominal obesity risk variants on adipocyte expression of more than 100 genes Open
Given the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral ad…
View article: QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples
QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples Open
Single-nuclei RNA sequencing remains a challenge for many human tissues, as incomplete removal of background signal masks cell-type-specific signals and interferes with downstream analyses. Here, we present Quality Clustering (QClus), a dr…
View article: An abdominal obesity missense variant in the adipocyte thermogenesis gene TBX15 is implicated in adaptation to cold in Finns
An abdominal obesity missense variant in the adipocyte thermogenesis gene TBX15 is implicated in adaptation to cold in Finns Open
Mechanisms of abdominal obesity GWAS variants have remained largely unknown. To elucidate these mechanisms, we leveraged subcutaneous adipose tissue (SAT) single nucleus RNA-sequencing and genomics data. After discovering that heritability…
View article: Single nucleus RNA-sequencing integrated into risk variant colocalization discovers 17 cell-type-specific abdominal obesity genes for metabolic dysfunction-associated steatotic liver disease
Single nucleus RNA-sequencing integrated into risk variant colocalization discovers 17 cell-type-specific abdominal obesity genes for metabolic dysfunction-associated steatotic liver disease Open
NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foun…
View article: Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity
Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity Open
Background Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our u…
View article: Targeting IL-1 controls refractory pityriasis rubra pilaris
Targeting IL-1 controls refractory pityriasis rubra pilaris Open
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared …
View article: Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease
Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease Open
View article: Technological advancements in functional interpretation of genome‐wide association studies ( <scp>GWAS</scp> ) findings: bridging the gap to clinical translation
Technological advancements in functional interpretation of genome‐wide association studies ( <span>GWAS</span> ) findings: bridging the gap to clinical translation Open
Genome‐wide association studies (GWAS) significantly advanced our understanding of the genetic underpinnings of diseases. However, challenges persist, particularly in interpreting non‐coding variants in linkage disequilibrium that affect g…
View article: Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis
Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis Open
BACKGROUND: While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological releva…
View article: Enhancing prediction accuracy of coronary artery disease through machine learning-driven genomic variant selection
Enhancing prediction accuracy of coronary artery disease through machine learning-driven genomic variant selection Open
View article: Progression of herpesvirus infection remodels mitochondrial organization and metabolism
Progression of herpesvirus infection remodels mitochondrial organization and metabolism Open
Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral …
View article: Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro
Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro Open
BACKGROUND: CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characteriz…
View article: The critical role of isomiRs in accurate differential expression analysis of miRNA-seq data
The critical role of isomiRs in accurate differential expression analysis of miRNA-seq data Open
MicroRNAs (miRNAs) are crucial for the regulation of gene expression and are promising biomarkers and therapeutic targets. miRNA isoforms (isomiRs) differ in their start/end offsets, which can impact the target gene selection and non-canon…
View article: Genetic variation drives differences in obesity-related gene regulation
Genetic variation drives differences in obesity-related gene regulation Open
Heikkinen and colleagues recently demonstrated that genetic variation, rather than dietary changes, governs gene regulation in liver. This finding highlights the impact of noncoding variants on chromatin accessibility, histone modification…
View article: ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling
ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling Open
Brain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7, and the long ncRNA Cyrano. We …
View article: Translatome profiling reveals <i>Itih4</i> as a novel smooth muscle cell–specific gene in atherosclerosis
Translatome profiling reveals <i>Itih4</i> as a novel smooth muscle cell–specific gene in atherosclerosis Open
Aims Vascular smooth muscle cells (SMCs) and their derivatives are key contributors to the development of atherosclerosis. However, studying changes in SMC gene expression in heterogeneous vascular tissues is challenging due to the technic…
View article: Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells
Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells Open
Vascular homeostasis and pathophysiology are tightly regulated by mechanical forces generated by hemodynamics. Vascular disorders such as atherosclerotic diseases largely occur at curvatures and bifurcations where disturbed blood flow acti…
View article: Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells
Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells Open