- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Reproductive Biology and Fertility
- Axon Guidance and Neuronal Signaling
- Cancer Genomics and Diagnostics
- Neurogenesis and neuroplasticity mechanisms
- Reproductive System and Pregnancy
- Animal Genetics and Reproduction
- T-cell and B-cell Immunology
- 3D Printing in Biomedical Research
- Hemoglobinopathies and Related Disorders
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- Angiogenesis and VEGF in Cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Immunotherapy and Biomarkers
- Neuroblastoma Research and Treatments
- Eosinophilic Disorders and Syndromes
- Reproductive Physiology in Livestock
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
Heidelberg University
2017-2025
German Cancer Research Center
2017-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2017-2025
DKFZ-ZMBH Alliance
2017-2022
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...
Eosinophils have been identified as a prognostic marker in immunotherapy of melanoma and suggested to contribute anti-tumor host defense. However, the influence immune checkpoint inhibitors (ICI) on eosinophil population is poorly studied. Here, we applied routine laboratory tests, multicolor flow cytometry, RNA microarray analysis, bio-plex assay analyze circulating eosinophils related serum inflammatory factors 32 patients treated with pembrolizumab or combination nivolumab ipilimumab. We...
Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential associated to dormancy. Here we identify the cell surface receptor neogenin-1 as specifically expressed in dormant HSCs. Loss of initially leads increased HSC expansion but subsequently loss and premature exhaustion vivo. Its ligand netrin-1 induces Egr1 expression maintains quiescence function cultured HSCs a Neo1 dependent manner. Produced arteriolar endothelial periarteriolar stromal cells, conditional...
Abstract The Four Core Genotypes (FCG) is a mouse model system used to disentangle the function of sex chromosomes and hormones. We report that copy 3.2 MB region X chromosome has translocated Y Sry- thus increased expression X-linked genes including single-stranded RNA sensor autoimmune disease mediator Tlr7 . This previously-unreported X-Y translocation complicates interpretation studies reliant on C57BL/6J FCG mice.
ABSTRACT In placental females, one copy of the two X chromosomes is largely silenced during a narrow developmental time window, in process mediated by non-coding RNA Xist 1 . Here, we demonstrate that can initiate X-chromosome inactivation (XCI) well beyond early embryogenesis. By modifying its endogenous level, show has capacity to actively silence genes escape XCI both neuronal progenitor cells (NPCs) and vivo , mouse embryos. We also plays direct role eliminating TAD-like structures...
Donor blood saves lives, yet the potential impact of recurrent large-volume phlebotomy on donor health and hematopoietic stem cells (HSCs) remains largely unexplored. In our study, we conducted a comprehensive screening 217 older male volunteer donors with history extensive donation (>100 life-time donations) to investigate phenomenon clonal hematopoiesis (CH). No significant difference in overall incidence CH was found frequent (FD) compared sporadic (<10 donations, 212...
Most genetic variants associated with human traits and diseases lie in noncoding regions of the genome 1, a key challenge is to determine which genes they affect 2,3. A common approach has been leverage associations between natural variation gene expression identify quantitative trait loci (eQTLs) population 4,5, while newer method uses pooled CRISPR interference (CRISPRi) perturbations single-cell transcriptome sequencing 6,7. Here, we systematically compared results from these approaches...
Abstract The Four Core Genotypes (FCG) is a mouse model system heavily used to disentangle the function of sex chromosomes and hormones. We report that copy 3.2 MB region X chromosome has translocated Y Sry- thus increased expression multiple genes including auto-immune master regulator Tlr7 . This previously-unreported X-Y translocation complicates interpretation studies reliant on FCG mice.
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 Cis- genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- trans- act across continuous trajectories cellular differentiation vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic at single-cell resolution an F1 hybrid mouse system, allowing for the comprehensive characterisation trans -genetic effects, including their dynamics differentiation. Collectively, almost half genes...
Abstract Hyperinnervation emerges as a common hallmark in the tumor microenvironment (TME) of most cancers, with clinical studies establishing direct link between increased innervation and poor prognosis. Despite acknowledged pivotal role TME, previous molecular profiling excluded tumor-infiltrating neurons due to unique anatomical characteristics peripheral neurons. While their axons extend into masses, DNA- mRNA-containing cell bodies reside adjacent ganglia, rendering them absent from...
Abstract Recurrent mutations in serine / arginine-rich splicing factor 2 (SRSF2), particularly the proline-to-histidine substitution at position 95 (P95H), have been proposed to drive neoplastic diseases. SRSF2 plays pivotal roles pre-mRNA processing and gene transcription. However, precise impact of these diverse functions on cancer cell behaviour remains unclear. Here, we show that deletion or homozygous P95H mutation both cause extensive DNA damage leading cycle arrest vitro vivo,...
Abstract Background Blood donation saves lives. Provided they are in good health, male volunteers can donate as often six times per year from the age of 18 into their late sixties. The burden blood is very unevenly distributed, with a small minority altruistic individuals providing this critical resource. While consequences persistent iron depletion donors have been studied context cancer and coronary heart disease, potential effects erythropoietic stress repetitive large-volume phlebotomy...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor entity with dismal prognosis. PDAC characterized by an extensive desmoplastic stroma and the microenvironment (TME) has been recognized to play crucial roles in development, therapy resistance, progression metastasis. Although different cell types of TME have molecularly analyzed, tumor-infiltrating neurons could not be considered so far, because their bodies are located adjacent ganglia peripheral nervous system...