Matthias Farlik
- Cutaneous lymphoproliferative disorders research
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Histiocytic Disorders and Treatments
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- T-cell and B-cell Immunology
- Extracellular vesicles in disease
- Pancreatic function and diabetes
- RNA regulation and disease
- Pancreatic and Hepatic Oncology Research
- interferon and immune responses
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Genetic Syndromes and Imprinting
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Cancer, Hypoxia, and Metabolism
- Pluripotent Stem Cells Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Medical University of Vienna
2019-2025
CeMM Research Center for Molecular Medicine
2015-2024
Austrian Academy of Sciences
2015-2024
KIIT University
2019
University of Vienna
2007-2012
Max Perutz Labs
2007-2012
Tissue-resident macrophages support embryonic development and tissue homeostasis repair. The mechanisms that control their differentiation remain unclear. We report here erythro-myeloid progenitors in mice generate premacrophages (pMacs) simultaneously colonize the whole embryo from day 9.5 a chemokine-receptor-dependent manner. core macrophage program initiated pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific early macrophages. This process...
Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show mouse trunk neural become biased toward neuronal lineages when they delaminate from the tube, whereas cranial acquire ectomesenchyme potential dependent on activation of transcription factor Twist1. The choices make to sensory, glial, autonomic, or mesenchymal can be formalized as a series sequential binary decisions. Each branch decision tree involves initial...
Methods for single-cell genome and transcriptome sequencing have contributed to our understanding of cellular heterogeneity, whereas methods epigenomics are much less established. Here, we describe a whole-genome bisulfite (WGBS) assay that enables DNA methylation mapping in very small cell populations (μWGBS) single cells (scWGBS). Our is optimized profiling many samples at low coverage, bioinformatic method analyzes collections methylomes infer cell-state dynamics. Using these...
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types a major aim regenerative medicine. One promising approach transdifferentiation developmentally related types, including glucagon-producing α cells. In genetic model, loss master regulatory transcription factor Arx sufficient to induce conversion functional β-like Here, we identify artemisinins as small molecules that functionally repress causing its...
Hematopoietic stem cells give rise to all blood in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used meta-epigenomic approach combines profiles across many small pools and performed single-cell methylome sequencing assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow,...
Scientific Report21 December 2015Open Access Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types Jin Li CeMM Research Center for Molecular Medicine the Austrian Academy Sciences, Vienna, Austria Search more papers by this author Johanna Klughammer Matthias Farlik Thomas Penz Andreas Spittler Medical University Anna Spiegel Forschungsgebäude, Charlotte Barbieux Department Surgery, Cell Isolation and Transplantation Center, Geneva Hospitals, Geneva,...
CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations MHC-I-restricted epitopes after deep sequencing of 747 isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding a cell-free vitro assay. Reduced mutant was associated with decreased proliferation, IFN-γ production cytotoxic activity cells isolated from HLA-matched patients. Single RNA ex vivo expanded, tetramer-sorted patients further...
Abstract Methylation of cytosines is a prototypic epigenetic modification the DNA. It has been implicated in various regulatory mechanisms across animal kingdom and particularly vertebrates. We mapped DNA methylation 580 species (535 vertebrates, 45 invertebrates), resulting 2443 genome-scale profiles multiple organs. Bioinformatic analysis this large dataset quantified association with underlying genomic sequence throughout vertebrate evolution. observed broadly conserved link two major...
Abstract Immune cells need to sustain a state of constant alertness over lifetime. Yet, little is known about the regulatory processes that control fluent and fragile balance called homeostasis. Here we demonstrate JAK-STAT signaling, beyond its role in immune responses, major regulator cell We investigated JAK-STAT-mediated transcription chromatin accessibility across 12 mouse models, including knockouts all STAT factors TYK2 kinase. Baseline signaling was detected CD8 + T macrophages...
Most genome-wide assays provide averages across large numbers of cells, but recent technological advances promise to overcome this limitation. Pioneering single-cell are now available for genome, epigenome, transcriptome, proteome, and metabolome profiling. Here, we describe how these different dimensions can be combined into multi-omics that comprehensive profiles the same cell.
Abstract Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibility maps 88 CLL samples from 55 patients measured the ATAC-seq assay. We also performed ChIPmentation and RNA-seq profiling ten representative samples. Based on resulting data set, devised applied bioinformatic method that links profiles to...
The most striking characteristic of CHO cells is their adaptability, which enables efficient production proteins as well growth under a variety culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution epigenetic modifications towards phenotype evolution, comprehensive genome epigenome data are presented for six related cell lines, both response to perturbations (different conditions media selection specific with increased transient...
Abstract Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels alanine transaminase (ALT), alkaline phosphatase (ALP) gamma-glutamyl transferase (GGT) using data 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent the Million Veteran Program, Rotterdam Study Lifeline study confirms 517 enzyme SNPs. Genetic risk score identified SNPs is strongly associated...
Hematopoietic stem cells (HSCs) sustain hematopoiesis throughout life. HSCs exit dormancy to restore hemostasis in response stressful events, such as acute blood loss, and must return a quiescent state prevent their exhaustion resulting bone marrow failure. HSC activation is driven part through the phosphatidylinositol 3-kinase (PI3K)/AKT/mTORC1 signaling pathway, but less known about cell-intrinsic pathways that control dormancy. Here, we delineate an ERK-dependent, rate-limiting feedback...
Abstract The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease. To define the underlining regulatory dynamics, we analyze high-resolution time courses of CLL, combining immune-phenotyping, single-cell transcriptome profiling, and chromatin mapping. We identify a consistent program starting sharp decrease NF-κB binding CLL cells, which is followed by reduced...
Abstract We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted islands. genomic predominantly transcription factor binding enhancer regions. Mendelian...
Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered presence an abundant population Schwann that persisted in scar tissue after wound healing. In contrast normal skin, show a unique, pro-fibrotic phenotype. Our data support hypothesis contribute formation extracellular matrix able affect M2 polarization...