A5028715904- Single-cell and spatial transcriptomics
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Multiple Myeloma Research and Treatments
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Mesenchymal stem cell research
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- Immune responses and vaccinations
- Pulmonary Hypertension Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Molecular Biology Techniques and Applications
- Platelet Disorders and Treatments
Heidelberg University
2016-2025
German Cancer Society
2024-2025
Charité - Universitätsmedizin Berlin
2018-2025
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2018-2025
Max Delbrück Center
2018-2025
Deutschen Konsortium für Translationale Krebsforschung
2018-2025
University Hospital Heidelberg
2008-2025
Queen Mary University of London
2024-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2015-2024
DKFZ-ZMBH Alliance
2015-2024
Highlights•Myc-depleted ESCs exhibit reversible biosynthetic dormancy and proliferation arrest•Myc expression is strongly reduced in hormonally induced diapause embryos•Myc mutant embryos have similar signatures•Myc depletion induces a reversible, pluripotent diapause-like state blastocystsSummaryMouse embryonic stem cells (ESCs) are maintained naive ground of pluripotency the presence MEK GSK3 inhibitors. Here, we show that ground-state express low Myc levels. Deletion both c-myc N-myc...
Abstract Single-cell genomics technology has transformed our understanding of complex cellular systems. However, excessive cost and a lack strategies for the purification newly identified cell types impede their functional characterization large-scale profiling. Here, we have generated high-content single-cell proteo-genomic reference maps human blood bone marrow that quantitatively link expression up to 197 surface markers identities biological processes across all main hematopoietic in...
Inter-patient variability and the similarity of healthy leukemic stem cells (LSCs) have impeded characterization LSCs in acute myeloid leukemia (AML) their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied samples from 19 AML patients, CloneTracer revealed routes differentiation. Although residual preleukemic dominated dormant cell compartment, active resembled counterpart retained erythroid...
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...
Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization these remains elusive with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic (LSCs) underlie mortality but are difficult isolate due their low abundance high similarity healthy hematopoietic (HSCs). Here, we demonstrate that LSCs, HSCs, pre-leukemic can be identified molecularly profiled by combining single-cell transcriptomics...
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...
The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. PTCL had clonal rearrangement, which was already detectable in the apheresis product CAR manufacturing and 7 months earlier autologous transplantation. Somatic
The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As disease progresses, malignant myeloma cells can evolve to survive outside marrow. However, processes underlying independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell spatial multiomics analyses marrow-confined intramedullary paired breakout lesions that disrupt cortical bone. These revealed distinct cellular architectural features lesions,...
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation substantially differs from effects triggered upon injection synthetic agents. In infections, inflammatory responses had to exceed local thresholds within bone...
In multiple myeloma spatial differences in the subclonal architecture, molecular signatures and composition of microenvironment remain poorly characterized. To address this shortcoming, we perform multi-region sequencing on paired random bone marrow focal lesion samples from 17 newly diagnosed patients. Using single-cell RNA- ATAC-seq find a median 6 tumor subclones per patient unique lesions. Genetically identical display different levels transcriptional plasticity, including nearly...
Abstract Background Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL). Methods Thirteen were treated escalating doses CD19-directed CARTs between 1 × 10 6 and 50 CARTs/m 2 . Leukapheresis, manufacturing...