A5073093050- Glioma Diagnosis and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Congenital Ear and Nasal Anomalies
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Plant tissue culture and regeneration
- Chromatin Remodeling and Cancer
- Immune cells in cancer
- Lymphatic System and Diseases
- Cancer Genomics and Diagnostics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Anesthesia and Neurotoxicity Research
- Ferroptosis and cancer prognosis
- Angiogenesis and VEGF in Cancer
- Tracheal and airway disorders
- Cancer, Lipids, and Metabolism
Heidelberg University
2016-2025
German Cancer Research Center
2016-2025
DKFZ-ZMBH Alliance
2014-2025
ShanghaiTech University
2023-2025
Deutschen Konsortium für Translationale Krebsforschung
2024
Shanghai Clinical Research Center
2024
Gerresheimer (Germany)
2023
Inner Mongolia University of Technology
2023
SAIC-GM (China)
2023
Sichuan University
2018
Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, heterogeneity regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry identified distinct senescence-like tetraspanin-8 (TSPAN8)
The tailless ( Tlx ) gene encodes an orphan nuclear receptor that is expressed by neural stem/progenitor cells in the adult brain of subventricular zone (SVZ) and dentate gyrus (DG). function stem SVZ remains largely unknown. We show here exclusively astrocyte-like B cells. An inducible mutation leads to complete loss neurogenesis. Furthermore, analysis indicates required for transition from radial glial These findings demonstrate crucial role generation maintenance NSCs vivo.
Malignant gliomas are the most common primary brain tumors, and associated with frequent resistance to therapy as well poor prognosis. Here we demonstrate that nuclear receptor tailless (Tlx), which in adult is expressed exclusively astrocyte-like B cells of subventricular zone, acts a key regulator neural stem cell (NSC) expansion tumor initiation from NSCs. Overexpression Tlx antagonizes age-dependent exhaustion NSCs mice leads migration stem/progenitor their natural niche. The increase...
Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 granule neuron progenitors leads to hypoplasia mice, due impairment differentiation, induction apoptosis and abnormal localization Purkinje cells, which closely recapitulates known clinical features cerebella...
Abstract YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions sufficient to drive malignant transformation mice, and resulting tumors share histo-molecular characteristics human ependymomas. Nuclear localization protein is mediated by MAMLD1 independent YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses YAP1-MAMLD1-positive ependymoma reveal...
Abstract Glioblastoma frequently exhibits therapy-associated subtype transitions to mesenchymal phenotypes with adverse prognosis. Here, we perform multi-omic profiling of 60 glioblastoma primary tumours and use orthogonal analysis chromatin RNA-derived gene regulatory networks identify 38 master regulators, whose cell population-specific activities further map in published single-cell RNA sequencing data. These analyses the oligodendrocyte precursor marker modifier SOX10 as a regulator RTK...
Abstract Recent advances in the genomics of glioblastoma (GBM) led to introduction molecular neuropathology but failed translate into treatment improvement. This is largely attributed genetic and phenotypic heterogeneity GBM, which are considered major obstacle GBM therapy. Here, we use advanced human GBM-like organoid (LEGO: L aboratory E ngineered G lioblastoma-like O rganoid) models provide an unprecedented comprehensive characterization LEGO using single-cell transcriptome, DNA...
Abstract T cell receptor-engineered cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable antigen associated with stemness. Here, we identify therapeutic HLA-A*02-restricted PTPRZ1-reactive TCR retrieved from vaccinated patient. Single-cell sequencing primary brain tumors shows PTPRZ1 overexpression malignant cells, especially stem...
Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) accurately recapitulates the cellular molecular pathology of human brain tumors. Patient-derived explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling wide range tumors central...
Recently, we found strong overexpression of the mucin-type glycoprotein podoplanin (PDPN) in human astrocytic brain tumors, specifically primary glioblastoma multiforme (GB). In current study, show an inverse correlation between PDPN expression and PTEN levels GB glioma cell lines, report elevated protein subventricular zone tissue sections PTEN-deficient mice. cells lacking functional PTEN, reintroduction wild-type inhibition downstream target kinase B/AKT, or interference with...
Neuropeptides, such as neuropeptide S (NPS) and oxytocin (OXT), represent potential options for the treatment of anxiety disorders due to their potent anxiolytic profile. In this study, we aimed reveal mechanisms underlying behavioral action NPS, present a chain evidence that effects NPS within hypothalamic paraventricular nucleus (PVN) are mediated via actions on local OXT neurons in male Wistar rats. First, retrograde studies identified fibers originating brainstem locus coeruleus,...
Abstract Regulation of chromatin plays fundamental roles in the development brain. Haploinsufficiency remodeling enzyme CHD7 causes CHARGE syndrome, a genetic disorder that affects cerebellum. However, how controls states cerebellum remains incompletely understood. Using conditional knockout granule cell precursors mouse cerebellum, we find robustly promotes accessibility, active histone modifications, and RNA polymerase recruitment at enhancers. In vivo profiling genome architecture reveals...
Summary Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells ( NSPC s). An improved understanding underlying mechanisms that drive age‐associated neurogenic deficiency could lead development strategies alleviate cognitive facilitate neuroregeneration. essential step towards this aim is investigate molecular changes occur in on a genomewide scale. In study, we compare transcriptional, histone methylation DNA signatures s derived...
Glioblastoma (GBM) is described as a group of highly malignant primary brain tumors and stands one the most lethal malignancies. The genetic cellular characteristics GBM have been focal point ongoing research, revealing that it heterogeneous diseases with variations in RNA expression, DNA methylation, or composition. Despite wealth molecular data available, lack transferable pre-clinic models has limited application this information to disease classification rather than treatment...
Abstract Binding of the sialomucin-like transmembrane glycoprotein podoplanin (PDPN) to platelet receptor C-type lectin-like 2 induces activation and aggregation. In human high-grade gliomas, PDPN is highly expressed both in tumor cells tumor-associated astrocytes. glioma patients, high expression associated with worse prognosis has been shown correlate intratumoral aggregation an increased risk venous thromboembolism (VTE). To functionally assess role vivo, we established a syngeneic...
Glioblastomas (GBM) are the most aggressive tumors affecting central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM urgently needed for deciphering glioma biology and development of effective treatment options. The murine cell lines currently available engraftment immunocompetent mice not only exiguous but also inadequate representing prominent characteristics such as infiltrative behavior,...