A5064774607- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Blood Coagulation and Thrombosis Mechanisms
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- Vitamin K Research Studies
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Eosinophilic Disorders and Syndromes
- Platelet Disorders and Treatments
- Animal testing and alternatives
- melanin and skin pigmentation
- Gene expression and cancer classification
- Skin Protection and Aging
- Dermatology and Skin Diseases
- CAR-T cell therapy research
- Hemophilia Treatment and Research
- NF-κB Signaling Pathways
- Mesenchymal stem cell research
- IL-33, ST2, and ILC Pathways
RWTH Aachen University
2015-2024
Institute for Biomedical Engineering
2010-2023
Universitätsklinikum Aachen
2007
Maastricht University
2001-2006
Tissue factor (TF) plays an important role in hemostasis, inflammation, angiogenesis, and the pathophysiology of atherosclerosis cancer. In this article we uncover a mechanism which protein S, is well known as cofactor activated C, specifically inhibits TF activity by promoting interaction between full-length pathway inhibitor (TFPI) Xa (FXa). The stimulatory effect S on FXa inhibition TFPI caused 10-fold reduction K(i) FXa/TFPI complex, decreased from 4.4 nM absence to 0.5 presence S. This...
The study of changes in protein–DNA interactions measured by ChIP-seq on dynamic systems, such as cell differentiation, response to treatments or the comparison healthy and diseased individuals, is still an open challenge. There are few computational methods comparing signals with replicates. Moreover, none these previous approaches addresses specific experimental artefacts arising from studies biological We propose THOR, a Hidden Markov Model based approach, detect differential peaks...
Dendritic cells (DC) are professional antigen presenting that develop from hematopoietic stem through successive steps of lineage commitment and differentiation. Multipotent progenitors (MPP) committed to DC restricted common (CDP), which differentiate into specific subsets, classical (cDC) plasmacytoid (pDC). To determine epigenetic states regulatory circuitries during differentiation, we measured consecutive changes genome-wide gene expression, histone modification transcription factor...
Abstract Human induced pluripotent stem (iPS) cells can differentiate into of all three germ layers, including hematopoietic and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining for myeloid cells, dendritic (DC). Autosomal recessive or dominant IRF8 mutations occurring patients cause severe monocytic DC immunodeficiency. To study human we generated IRF8−/− iPS embryonic (ES) using RNA guided CRISPR/Cas9n genome...
This article is part of the Dendritic Cell Guidelines series, which provides a collection state-of-the-art protocols for preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization mouse human dendritic cells (DC) from lymphoid organs various non-lymphoid tissues. with top ticks pitfalls preparation successful generation DC different cellular sources, such as murine BM HoxB8 cells, well CD34+ cord blood, BM, peripheral blood or...
Dendritic cells (DCs) in lymphoid tissue comprise conventional DCs (cDCs) and plasmacytoid (pDCs) that develop from common DC progenitors (CDPs). CDPs are Flt3(+)c-kit(int)M-CSFR(+) reside bone marrow. In this study, we describe a two-step culture system recapitulates development c-kit(hi)Flt3(-/lo) multipotent (MPPs) into further cDC pDC subsets. MPPs amplified vitro with Flt3 ligand, stem cell factor, hyper-IL-6, insulin-like growth factor-1. The four-factor mixture readily induces...
DC s develop from multipotent progenitors ( MPP s), which commit into ‐restricted common dendritic cell CDP s). further differentiate classical (c s) and plasmacytoid (p Here, we studied the impact of histone acetylation on development in C 57 BL /6 mice by interfering with deacetylation, employing deacetylase HDAC ) inhibitors. We observed that commitment was attenuated inhibition p specifically blocked. Gene expression profiling revealed prevents establishment a ‐specific gene repertoire....
Transcription factors play a determining role in lineage commitment and cell differentiation. Interferon regulatory factor 8 (IRF8) is transcription hematopoiesis master regulator of dendritic cells (DC), an important immune for immunity tolerance. IRF8 prominently upregulated DC development by autoactivation controls both differentiation function. However, it unclear how Irf8 controlled eventually limited. Here, we identified novel long non-coding RNA transcribed from the +32 kb enhancer...
Abstract Motivation: Detection of changes in deoxyribonucleic acid (DNA)–protein interactions from ChIP-seq data is a crucial step unraveling the regulatory networks behind biological processes. The simplest variation this problem differential peak calling (DPC) problem. Here, one has to find genomic regions with signal between two cellular conditions interaction protein DNA. great majority methods can only analyze at time and are unable perform DPC. Recently, few approaches based on...
The TGF-β signaling pathway is a fundamental in the living cell, which plays key role many central cellular processes. complex and sometimes contradicting mechanisms by yields phenotypic effects are not yet completely understood. In this study we investigated compared transcriptional response profile of TGF-β1 stimulation different cell types. For purpose, extensive experiments performed time-course microarray data generated human mouse parenchymal liver cells, mesenchymal stromal cells...
The myeloproliferative disease polycythemia vera (PV) driven by the JAK2 V617F mutation can transform into myelofibrosis (post-PV-MF). It remains an open question how in hematopoietic stem cells induces MF. Megakaryocytes are major players murine PV models but difficult to study human setting. We generated induced pluripotent (iPSCs) from patients and differentiated them megakaryocytes. In differentiation assays, iPSCs recapitulated pathognomonic skewed megakaryocytic erythroid...
Protein S, the cofactor of activated protein C (APC), also expresses anticoagulant activity independent APC by directly inhibiting prothrombin activation via interactions with factor Xa, Va, and phospholipids. In different studies, however, large variations in APC-independent activities have been reported for S. The investigation presented here shows that within purified S preparations forms are present, which a hitherto unrecognized form (<5% total S) binds high affinity to phospholipid...
Graphical Abstract Patient-specific iPS cells with JAK2 V617F mutation differentiate into DC3 dendritic cells, megakaryocytes and red blood cells.
Abstract This article is part of the Dendritic Cell Guidelines series, which provides a collection state‐of‐the‐art protocols for preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization mouse human dendritic cells (DC) from lymphoid organs various nonlymphoid tissues. DC are sentinels immune system present in almost every mammalian organ. Since they represent rare cell population, need to be extracted with that specifically...
Abstract Langerhans cells (LC) represent the cutaneous contingent of dendritic (DC). Their development critically depends on transforming growth factor β1 (TGF‐β1) as demonstrated by analysis TGF‐β1 –/– mice, which lack LC. Here we used a two‐step culture system and transcriptional profiling DNA microarrays to search for target genes in DC. The study identified interferon regulatory 8 (IRF‐8) novel gene signaling effectively induced Smad2/3 phosphorylation IRF‐8 RNA protein expression....
We have recently described two types of Langerhans cells (LCs), which develop via separate pathways in steady-state conditions and during inflammation. Here, we propose that these LCs differ their requirement for transforming growth factor β1 (TGFβ1), discuss how TGFβ1 impacts on the development other dendritic cell subtypes.
Abstract Activating mutations leading to ligand-independent signaling of the stem cell factor receptor KIT are associated with several hematopoietic malignancies. One most common alterations is D816V mutation. In this study, we characterized mice, which conditionally express humanized in adult system determine pathological consequences unrestrained during blood development. We found that mutant animals acquired a myeloproliferative neoplasm similar polycythemia vera, marked by massive...