A5059873000- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Cancer-related molecular mechanisms research
- Rheumatoid Arthritis Research and Therapies
- RNA Research and Splicing
- RNA modifications and cancer
- Immunodeficiency and Autoimmune Disorders
- Cancer Genomics and Diagnostics
- Inflammatory Myopathies and Dermatomyositis
- Advanced Biosensing Techniques and Applications
- Bioinformatics and Genomic Networks
- Chronic Lymphocytic Leukemia Research
- Cancer Cells and Metastasis
- Cytokine Signaling Pathways and Interactions
- Molecular Biology Techniques and Applications
- Gene Regulatory Network Analysis
- Wnt/β-catenin signaling in development and cancer
- Advanced biosensing and bioanalysis techniques
- Cell Adhesion Molecules Research
- Genetic Associations and Epidemiology
- Virus-based gene therapy research
Karolinska Institutet
2015-2024
Karolinska University Hospital
2014-2022
Ludwig Cancer Research
2011-2020
Sahlgrenska University Hospital
2014
Moffitt Cancer Center
2014
University of Gothenburg
2014
Ludwig Cancer Research
2013-2014
KTH Royal Institute of Technology
2008
Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide single cells are lacking. Here, we present global across individual mouse preimplantation embryos mixed background (CAST/EiJ × C57BL/6J). We discovered abundant (12 to 24%) monoallelic autosomal genes and that the two occurs independently. The appeared random dynamic because there was considerable variation among closely related embryonic...
The parts of the genome transcribed by a cell or tissue reflect biological processes and functions it carries out. We characterized features mammalian transcriptomes at gene level through analysis RNA deep sequencing (RNA-Seq) data across human mouse tissues lines. observed that roughly 8,000 protein-coding genes were ubiquitously expressed, contributing to around 75% all mRNAs message copy number in most tissues. These encoded proteins often intracellular, tended be involved metabolism,...
Pluripotent embryonic stem (ES) cells can generate all cell types, but how lineages are initially specified and maintained during development remains largely unknown. Different classes of Sox transcription factors expressed neurogenesis have been assigned important roles from early lineage specification to neuronal differentiation. Here we characterize the genome-wide binding for Sox2, Sox3, Sox11, which vital functions in ES cells, neural precursor (NPCs), maturing neurons, respectively....
Developmental transcription factors important in early neuron specification and differentiation often remain expressed the adult brain. However, how these function to mantain appropriate neuronal identities neurons factor dysregulation may contribute disease largely unknown. The Nurr1 has been associated with Parkinson's is essential for development of ventral midbrain dopamine (DA) neurons. We used conditional gene-targeted mice which ablated selectively mature DA by treatment tamoxifen....
Although the locations of promoters and enhancers have been identified in several cell types, we still limited information on their connectivity. We developed HiCap, which combines a 4-cutter restriction enzyme Hi-C with sequence capture promoter regions. Applying method to mouse embryonic stem cells, promoter-anchored interactions involving 15,905 71,984 distal The regions were enriched for enhancer marks transcription, had mean fragment size only 699 bp--close single-enhancer resolution....
Notch signaling is frequently hyperactivated in breast cancer, but how the enhanced contributes to tumor process less well understood. In this report, we identify proinflammatory cytokine interleukin-6 (IL-6) as a novel target cells. Enhanced upregulated IL-6 expression, leading activation of autocrine and paracrine Janus kinase/signal transducers activators transcription signaling. upregulation was mediated by non-canonical signaling, it could be effectuated cytoplasmically localized...
Objective Antibodies against posttranslationally modified proteins are a hallmark of rheumatoid arthritis ( RA ), but the emergence and pathogenicity these autoantibodies still incompletely understood. The aim this study was to analyze antigen specificities mutation patterns monoclonal antibodies mA b) derived from synovial plasma cells address question cross‐reactivity. Methods IgG‐secreting were isolated fluid, variable regions immunoglobulins sequenced (n = 182) expressed in full‐length b...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory cells and elevated levels autoantibodies. Belimumab monoclonal antibody targeting the cytokine BAFF (a.k.a. BLyS), approved for treatment SLE.In this prospective cohort study, from peripheral blood 23 SLE patients initiating belimumab followed longitudinally up to three years, were assessed using mass cytometry.B decreased during study...
Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes Notch ligand, although it not clear how these contribute to disease development. We aimed develop mouse model of elucidate mechanisms.Mice missense mutation (H268Q) Jag1 (Jag1+/Ndr mice) were outbred C3H/C57bl6 background generate for (Jag1Ndr/Ndr mice)....
The clinical efficacy of B cell targeting therapies highlights the pathogenic potential cells in inflammatory diseases. Expression Fc Receptor like 4 (FcRL4) identifies a memory subset, which is enriched joints patients with rheumatoid arthritis (RA) and mucosa-associated lymphoid tissue. high level RANKL production by this subset indicates unique role. In addition, recent work has identified role for FcRL4 as an IgA receptor, suggesting function mucosal immunity. Here, contribution FcRL4+...
Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin as a 1p36.2 tumor suppressor. However, mechanism of suppression is unknown. We found that isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation DHX9, followed by subsequent induction proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma neuroblastoma arise from neural crest progenitors compete for growth factors such...
OBJECTIVE: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results been discrepant with few successful replications. Our objective was build a biobank DNA, RNA and protein measurements test the claim that current state-of-the-art precision medicine will RA patients. METHODS: We collected 451 blood samples 61 healthy individuals 185 initiating treatment, before treatment initiation at 3 month...
Abstract Analyses of transcriptional bursting from single-cell RNA-sequencing data have revealed patterns variation and regulation in the kinetic parameters that could be inferred. Here we profiled newly transcribed (4-thiouridine-labelled) RNA across 10,000 individual primary mouse fibroblasts to more broadly infer kinetics coordination. We demonstrate inference new profiles separate together specify burst size, synthesis rate (and not off rate) controls size. Importantly,...
Idiopathic inflammatory myopathies (IIM) are rare autoimmune systemic diseases characterized by muscle weakness and the presence of muscle-infiltrating T cells. IIM represent a clinical challenge due to heterogeneity symptoms variability response immunosuppressive treatment. Here, we performed in-depth single-cell sequencing on cells peripheral blood memory in six patients with recently diagnosed IIM. We identified tissue resident T-cell (TRM ) signatures including expression HOBIT, XCL1...
Neonatal hypoxia-ischemia (HI) is a major cause of perinatal death and long-term disabilities worldwide. Post-ischemic neuroinflammation plays pivotal role in HI pathophysiology. In the present study, we investigated temporal dynamics microglia (CX3CR1
Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, I diabetes, and inflammatory bowel disease. However, functional consequences of these are poorly characterized. Herein, we show blood cells that PTPN2 highly correlated DNA methylation levels at four CpG sites downstream expression long non-coding RNA (lncRNA) LINC01882 sites. We observed is mainly expressed T anti-CD3/CD28...
Abstract The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number studies exploring function in T cells, exact impact on T‐cell humans still unclear. In this study, using RNA sequencing, we show that, upon TCR‐activation, naïve human CD4 + cells homozygous for overexpress set genes CFLAR and 4‐1BB , which are important cytotoxic differentiation. Moreover, protein expression T‐box transcription factor...
As next generation sequencing technologies are getting more efficient and less expensive, RNA-Seq is becoming a widely used technique for transcriptome studies. Computational analysis of data often starts with the mapping millions short reads back to genome or transcriptome, process in which some found map equally well multiple genomic locations (multimapping reads). We have developed Minimum Unique Length Tool (MULTo), framework comprehensive representation mappability information, through...