A5038253305- Single-cell and spatial transcriptomics
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Immune Cell Function and Interaction
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Erythrocyte Function and Pathophysiology
- Reproductive Biology and Fertility
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Protein Degradation and Inhibitors
- Immune Response and Inflammation
- Cancer Genomics and Diagnostics
- Mesenchymal stem cell research
- Peptidase Inhibition and Analysis
- Reproductive Physiology in Livestock
- Endoplasmic Reticulum Stress and Disease
- Sphingolipid Metabolism and Signaling
- Erythropoietin and Anemia Treatment
- Immune responses and vaccinations
- Advanced Proteomics Techniques and Applications
- Virus-based gene therapy research
- Sarcoma Diagnosis and Treatment
DKFZ-ZMBH Alliance
2019-2024
German Cancer Research Center
2019-2024
Heidelberg University
2019-2024
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2019-2024
Max Delbrück Center
2023
Heidelberg University
2022
The female reproductive tract (FRT) undergoes extensive remodeling during cycling. This recurrent and how it shapes organ-specific aging remains poorly explored. Using single-cell spatial transcriptomics, we systematically characterized morphological gene expression changes occurring in ovary, oviduct, uterus, cervix, vagina at each phase of the mouse estrous cycle, decidualization, into aging. These analyses reveal that fibroblasts play central-and highly organ-specific-roles FRT by...
For many diseases there are delays in diagnosis due to a lack of objective biomarkers for disease onset. Here, 41,931 individuals from the United Kingdom Biobank Pharma Proteomics Project, we integrated measurements ~3,000 plasma proteins with clinical information derive sparse prediction models 10-year incidence 218 common and rare (81-6,038 cases). We then compared developed using proteomic data either basic alone or combined 37 assays. The predictive performance including as few 5 20 was...
Activated SUMOylation is a hallmark of cancer. Starting from targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function activated SUMOylation, which attenuated the immunogenicity tumor cells. allowed cancer cells to evade CD8+ T cell-mediated immunosurveillance by suppressing MHC class I (MHC-I) antigen-processing and presentation machinery (APM). Loss MHC-I APM frequent cause resistance immunotherapies, pharmacological inhibition...
Abstract The neoplastic stromal cells of giant cell tumor bone (GCTB) carry a mutation in H3F3A , leading to mutant histone variant, H3.3-G34W, as sole recurrent genetic alteration. We show that patient-derived H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on DNA methylation, accessibility modification level, can be partially recapitulated an orthogonal line system by introduction H3.3-G34W. These affect mainly heterochromatic bivalent...
Abstract Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory and bacterial compromise competitive HSC capacity cause bone marrow (BM) failure. However, our understanding how HSCs act during acute contained remains incomplete. Here, we used advanced chimeric genetic mouse models in combination...
Abstract Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well new therapies are therefore highly needed. The proteome has not been systematically assessed before holds potential to uncover insight into disease biology improved prognostication in addition genetic transcriptomic studies. Here we provide comprehensive multiomics analysis including deep tandem mass tag-based quantitative...
Hematopoietic stem and progenitor cells (HSPCs) are known to respond acute inflammation; however, little is understood about the dynamics heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during sensing, response, recovery phases inflammatory response HSPCs treatment (a total 10,046 from four time points spanning first 72 h response) with pro-inflammatory cytokine IFNα investigate HSPCs' dynamic changes inflammation. We developed essential novel...
Abstract Chromosomal instability is a major driver of intratumoral heterogeneity (ITH), promoting tumor progression. In the present study, we combined structural variant discovery and nucleosome occupancy profiling with transcriptomic immunophenotypic changes in single cells to study ITH complex karyotype acute myeloid leukemia (CK-AML). We observed landscapes within individual patients CK-AML characterized by linear circular breakage–fusion–bridge cycles chromothripsis. identified three...
SUMMARY The bone marrow (BM) constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular composition spatial organization into distinct ‘niches’ remains controversial. Here, we combine single-cell spatially resolved transcriptomics to systematically map molecular of endosteal, sinusoidal, arteriolar BM niches. This allowed us transcriptionally profile all major resident cell types, determine their localization, clarify sources key growth...
The female reproductive tract (FRT) undergoes extensive remodeling during each cycle, regulated by systemic changes in sex hormones. Whether this recurrent influences a specific organ’s aging trajectory is unknown. To address this, we systematically characterized at single-cell resolution the morphological and transcriptional that occur ovary, oviduct, uterus, cervix, vagina phase of mouse estrus decidualization, into aging. Transcriptional cell-to-cell communication networks cycle are...
Abstract The long-term consequences of cancer or therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we have performed an in-depth characterization bone marrow ecosystem multiple myeloma survivors at initial diagnosis and up to 17 following survival. Using comparative single-cell analyses in combination with molecular, genomic functional approaches, demonstrate that display pronounced alterations their microenvironment associated impaired...
Hematopoietic stem and progenitor cells (HSPCs) are known to respond acute inflammation; however, little is understood about the dynamics heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing HSPCs during sensing, response recovery phases inflammatory treatment with pro-inflammatory cytokine IFNα investigate HSPCs’ dynamic changes inflammation. For analysis resulting datasets, developed a computational pipeline for time series. Using semi-supervised...
Abstract The long-term consequences of cancer and its therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we present an in-depth characterization bone marrow ecosystem multiple myeloma survivors, from initial diagnosis up to 17 following a single line survival. Using comparative single-cell analyses combined with molecular, genomic, functional approaches, demonstrate that survivors exhibit pronounced alterations in their microenvironment...
Background: Multiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, it remains incurable and better risk stratification as well new therapies are therefore highly needed. While genomic alterations gene expression profiles have been extensively studied that led to insights into disease biology improved prognostic models, proteome multiple has not systematically assessed. Aims: To provide comprehensive multi-omics analysis malignancies. Methods: Samples...
Background: Acute myeloid leukemia (AML) with complex karyotype (CK) is a heterogenous AML subgroup dismal response to standard treatment. CK-AML has remained poorly characterized at the molecular level, mainstream techniques struggling unravel complexity of structural variants (SVs) and link them phenotypic characteristics. To improve our understanding dynamics in CK-AML, we established an integrated single cell multi-omics approach that combines analysis SVs nucleosome occupancy (NO)...
Background: Chronic infections in mice have been shown to lead an increased proliferation of the hematopoietic stem and progenitor cell (HSPCs) compartment a subsequent loss function. However, many these infection-models involve challenging with very high dose purified pathogen administered via non-physiologic route, thereby not recapitulating natural infection/colonization process. Recent studies from Rosshart et al (PMID: 31371577) has led generation so-called “wildling” that carry full...