A5080731852- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Immune cells in cancer
- Cancer Cells and Metastasis
- Gene expression and cancer classification
- T-cell and B-cell Immunology
- Congenital heart defects research
- Systemic Lupus Erythematosus Research
- Microbial Community Ecology and Physiology
- Cancer-related molecular mechanisms research
- Neuroinflammation and Neurodegeneration Mechanisms
- Digestive system and related health
- RNA Research and Splicing
- Gut microbiota and health
- Inflammatory Bowel Disease
- SARS-CoV-2 and COVID-19 Research
- Advanced Fluorescence Microscopy Techniques
- IL-33, ST2, and ILC Pathways
- Advanced Biosensing Techniques and Applications
- Evolution and Genetic Dynamics
- Tissue Engineering and Regenerative Medicine
- Monoclonal and Polyclonal Antibodies Research
- Rheumatoid Arthritis Research and Therapies
KTH Royal Institute of Technology
2018-2025
Science for Life Laboratory
2018-2025
Stockholm University
2022
Karolinska Institutet
2021
ORCID
2021
Karolinska University Hospital
1958
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics multiplexed ion beam imaging from a series human cSCCs matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating epidermal states, tumor-specific keratinocyte (TSK) population unique to cancer, which localized fibrovascular niche. Integration data mapped ligand-receptor networks specific types, revealing...
Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression throughout a multifocal prostate using spatial transcriptomics (ST) technology. Utilizing novel approach for deconvolution, analyze transcriptomes nearly 6750 tissue regions and extract distinct profiles different components, such as stroma, normal PIN glands, immune cells cancer. We distinguish healthy diseased areas thereby provide insight into changes...
ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated...
Abstract In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions their functional relevance. To address this, we investigate gene expression HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven annotation assessment intra- interpatient heterogeneity;...
Abstract Background Recent advancements in situ gene expression technologies constitute a new and rapidly evolving field of transcriptomics. With the recent launch 10x Genomics Visium platform, such methods have started to become widely adopted. The experimental protocol is conducted on individual tissue sections collected from larger sample. two-dimensional nature this data requires multiple consecutive be sample order construct comprehensive three-dimensional map tissue. However, there...
Abstract Defining the transition from benign to malignant tissue is fundamental improving early diagnosis of cancer 1 . Here we use a systematic approach study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics 2 infer copy number variations >120,000 regions across multiple organs, tissues. demonstrate that genome-wide variation reveals distinct patterns within tumours nearby using an organ-wide focused on...
Abstract Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding the spatial liver transcriptome in recent years. However, global differences across lobular units remain elusive physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis sectioned tissue. We confirm that this complex tissue is predominantly determined by zonation. By introducing novel computational approaches, enable gradient...
Abstract The intestinal barrier is composed of a complex cell network defining highly compartmentalized and specialized structures. Here, we use spatial transcriptomics to define how the transcriptomic landscape spatially organized in steady state healing murine colon. At conditions, demonstrate previously unappreciated molecular regionalization colon, which dramatically changes during mucosal healing. identified spatially-organized transcriptional programs healing, regions with dominant...
Abstract The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds molecularly diverse cell types in the nervous system, but lineage relationships between mature and are not well understood. Here we show vivo barcoding early progenitors to simultaneously profile phenotypes clonal relations mouse using single-cell spatial transcriptomics. By reconstructing thousands clones, discovered...
We present a spatial omics approach that combines histology, mass spectrometry imaging and transcriptomics to facilitate precise measurements of mRNA transcripts low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. demonstrate the potential our method using mouse human brain samples in context dopamine Parkinson's disease.
Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here, we report a procedure to perform genome-wide spatial analysis of mRNA in FFPE-fixed sections, using well-established, commercially available methods for imaging and barcoding slides spotted with barcoded oligo(dT) probes capture 3′ end molecules sections. We applied this method expression profiling cell type mapping coronal sections from mouse brain demonstrate method's capability...
Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue remains an unmet challenge. To gain insight into process mucosal healing, we longitudinally examined immune cell composition during damage and regeneration. B cells were dominant type in healing colon, single-cell RNA sequencing (scRNA-seq) revealed expansion IFN-induced subset experimental predominantly located damaged areas associated with colitis severity....
Abstract The inflamed rheumatic joint is a highly heterogeneous and complex tissue with dynamic recruitment expansion of multiple cell types that interact in multifaceted ways within localized area. Rheumatoid arthritis synovium has primarily been studied either by immunostaining or molecular profiling after homogenization. Here, we use Spatial Transcriptomics, where tissue-resident RNA spatially labeled situ barcodes transcriptome-wide fashion, to study local interactions at the site...
Abstract Spatially resolved transcriptomics has enabled precise genome-wide mRNA expression profiling within tissue sections. The performance of methods targeting the polyA tails relies on availability specimens with high RNA quality. Moreover, cost currently available spatial assays requires a careful sample screening process to increase chance obtaining high-quality data. Indeed, upfront analysis quality can show considerable variability due handling, storage, and/or intrinsic factors. We...
Abstract The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis single-cell and spatial multi-omics data, we used 16 prenatal samples to create a comprehensive developmental atlas during post-conceptional weeks 5–12. This revealed how commitment neural progenitor cells their positioning are spatiotemporally regulated specific gene sets. We identified unique events development...
Spatially resolved transcriptomics technologies generate gene expression data with retained positional information from a tissue section, often accompanied by corresponding histological image. Computational tools should make it effortless to incorporate spatial into analyses and present analysis results in their context. Here, we semla, an R package for processing, analysis, visualization of spatially generated the Visium platform, that includes interactive web applications exploration...
The spatial distribution of cell surface proteins governs vital processes the immune system such as intercellular communication and mobility. However, fluorescence microscopy has limited scalability in multiplexing throughput needed to drive proteomics discoveries at subcellular level. We present Molecular Pixelation (MPX), an optics-free, DNA sequence-based method for single cells using antibody-oligonucleotide conjugates (AOCs) DNA-based, nanometer-sized molecular pixels. relative...