A5036562744- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Asthma and respiratory diseases
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- Respiratory viral infections research
- COVID-19 Clinical Research Studies
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Cell Adhesion Molecules Research
- Pluripotent Stem Cells Research
- Extracellular vesicles in disease
Karolinska Institutet
2020-2024
Linköping University Hospital
2014-2024
Linköping University
2013-2020
University of Zurich
2018
SIB Swiss Institute of Bioinformatics
2018
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is commonly diagnosed reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA in patient samples, but extraction constitutes a major bottleneck current testing. Methodological simplification could increase diagnostic availability and efficiency, benefitting care infection control. Here, we describe methods circumventing COVID-19 testing performing RT-PCR directly...
Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host and interpret disease pathogenesis. Natural killer (NK) cells are effector lymphocytes that respond acute viral infections but might also contribute immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets peripheral blood patients. This pattern was mirrored scRNA-seq signatures bronchoalveolar lavage from Unsupervised high-dimensional analysis...
Abstract The Notch signaling pathway has fundamental roles in embryonic development and the nervous system. current model of receptor activation involves initiation via a force-induced conformational change. Here, we define conditions that reveal pulling force-independent using soluble multivalent constructs. We treat neuroepithelial stem-like cells with molecularly precise ligand nanopatterns displayed from solution DNA origami. follows clusters Jag1, chimeric structures where most Jag1...
The DNA methylation profiles of mammalian cell lines differ from those the primary tissues which they were derived, exhibiting increasing divergence in vivo profile with extended time culture. Few studies have directly examined initial epigenetic and transcriptional consequences adaptation cells to culture, potential mechanisms through this dysregulation occurs is unknown.We demonstrate that mouse embryonic fibroblasts culture results a rapid reprogramming states. We observed global...
Technical errors have resulted in the false discovery of DNA modification N 6 -methyladenine mammals.
Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets complex diseases, but is complicated by involvement of thousands variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows characterization such changes in whole organs. The based on applying network tools to organize analyze scRNA-seq data from a mouse model arthritis human rheumatoid arthritis, order find diagnostic therapeutic targets....
Human uterine NK cells continuously differentiate in response to the monthly regeneration of endometrium and during pregnancy.
X-chromosome inactivation and X-upregulation are the fundamental modes of chromosome-wide gene regulation that collectively achieve dosage compensation in mammals, but regulatory link between two remains elusive dynamics unknown. Here, we use allele-resolved single-cell RNA-seq combined with chromatin accessibility profiling finely dissect their separate effects on RNA levels during mouse development. Surprisingly, uncover elastically tunes expression a sex- lineage-specific manner, moreover...
Abstract Insulin binds the insulin receptor (IR) and regulates anabolic processes in target tissues. Impaired IR signalling is associated with multiple diseases, including diabetes, cancer neurodegenerative disorders. IRs have been reported to form nanoclusters at cell membrane several types, even absence of binding. Here we exploit nanoscale spatial organization achieve controlled multivalent activation. To control valency, developed rod-like insulin–DNA origami nanostructures carrying...
Excitatory projections from the lateral hypothalamic area (LHA) to habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification define structural and functional heterogeneity of LHA-LHb pathway. Our identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles projection patterns. found that genetically defined neurons signal distinct aspects emotional or naturalistic behaviors, such as estrogen...
Altered DNA methylation patterns in CD4+ T-cells indicate the importance of epigenetic mechanisms inflammatory diseases. However, identification these alterations is complicated by heterogeneity most Seasonal allergic rhinitis (SAR) an optimal disease model for study because its well-defined phenotype and etiology. We generated genome-wide (Npatients = 8, Ncontrols 8) gene expression 9, 10) profiles from SAR patients healthy controls using Illumina's HumanMethylation450 HT-12 microarrays,...
Early regulators of disease may increase understanding mechanisms and serve as markers for presymptomatic diagnosis treatment. However, early are difficult to identify because patients generally present after they symptomatic. We hypothesized that T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in cell differentiation prioritizing hub TFs were enriched disease-associated polymorphisms. A gene regulatory network (GRN) was constructed time series...
ABSTRACT Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method of COVID-19 diagnostics a reverse transcription polymerase chain reaction (RT-PCR) assay, to detect presence SARS-CoV-2 RNA in patient samples, typically from nasopharyngeal swabs. extraction major bottleneck current testing, terms turn-around, logistics, component availability and cost, which delays or completely precludes many settings....
Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy resulting from overproduction of immature T-cells in the thymus and typified by widespread alterations DNA methylation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development targeted therapies prevent relapse key improving prognosis. Whereas mutations demethylating enzyme TET2 are frequent adult malignancies, rare. Here, we analyzed RNA-sequencing data 321 primary T-ALLs, 20 cell lines, 25...
BackgroundThroughout the SARS-CoV-2 pandemic, multiple waves of variants concern have swept across populations, leading to a chain new and yet more contagious dominating COVID-19 cases. Here, we tracked remarkably rapid shift from Omicron BA.1 BA.2 sublineage dominance in Swedish population early 2022 at day-by-day basis.MethodsUsing custom lineage-typing RT-PCR assay, analyzed 174,933 clinical upper airway samples collected during January March 2022.FindingsOur study demonstrates...
Understanding innate immune responses in COVID-19 is important for deciphering mechanisms of host and interpreting disease pathogenesis. Natural killer (NK) cells are effector lymphocytes that respond to acute viral infections, but might also contribute pathology. Here, using 28-color flow cytometry, we describe a state strong NK cell activation across distinct subsets peripheral blood patients, pattern mirrored scRNA-seq signatures lung cells. Unsupervised high-dimensional analysis...
Abstract Sex-chromosome dosage represents a challenge for heterogametic species to maintain correct proportion of gene products across chromosomes in each sex. While therian mammals (XX/XY system) achieve near-perfect balance X-chromosome mRNAs through X-upregulation and X-inactivation, birds (ZW/ZZ have been found lack efficient compensation at RNA level, challenging the necessity resolving major gene-dosage discrepancies avian cells. Through allele-resolved multiome analyses, we...
Abstract Throughout the SARS-CoV-2 pandemic, multiple waves of variants concern have swept across populations, leading to a chain new and yet more contagious lineages dominating COVID-19 cases. Here, we tracked remarkably rapid shift from Omicron BA.1 BA.2 sub-variant dominance in Swedish population during January–March 2022. By analysis 174,933 clinical nasopharyngeal swab samples using custom variant-typing RT-PCR assay, uncover nearly two-fold higher levels viral RNA cases with BA.2....
Abstract Joint single-cell measurements of gene expression and DNA regulatory element activity holds great promise as a tool to understand transcriptional regulation. Towards this goal we have developed Smart3-ATAC, highly sensitive method which allows joint mRNA chromatin accessibility analysis genome wide in single cells. With are able obtain the highest possible quality per cell. The combines transcriptomic profiling based on Smart-seq3 protocol cytosolic mRNA, with novel low-loss ATAC...