A5071578599- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Genetic Neurodegenerative Diseases
- Renal and related cancers
- Mitochondrial Function and Pathology
- Chemical synthesis and alkaloids
- Neural dynamics and brain function
- Microtubule and mitosis dynamics
- Psychedelics and Drug Studies
- Anesthesia and Neurotoxicity Research
- Nuclear Receptors and Signaling
- Hippo pathway signaling and YAP/TAZ
- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Phagocytosis and Immune Regulation
- Fetal and Pediatric Neurological Disorders
German Cancer Research Center
2018-2025
Heidelberg University
2018-2025
University Hospital Heidelberg
2018-2025
Central Institute of Mental Health
2018-2025
University of Bonn
2009-2022
University Hospital Bonn
2019-2022
Life & Brain (Germany)
2008-2019
StemCells (United States)
2019
Hertie Foundation
2008-2018
Scripps Research Institute
2009
An intriguing question in human embryonic stem cell (hESC) biology is whether these pluripotent cells can give rise to stably expandable somatic cells, which are still amenable extrinsic fate instruction. Here, we present a pure population of long-term self-renewing rosette-type hESC-derived neural (lt-hESNSCs), exhibit extensive self-renewal, clonogenicity, and stable neurogenesis. Although lt-hESNSCs show restricted expression regional transcription factors, they retain responsiveness...
Reprogramming of adult human somatic cells to induced pluripotent stem (iPSCs) is a novel approach produce patient-specific for autologous transplantation. Whether such survive long-term, differentiate functional neurons, and induce recovery in the stroke-injured brain are unclear. We have transplanted long-term self-renewing neuroepithelial-like cells, generated from fibroblast-derived iPSCs, into stroke-damaged mouse rat striatum or cortex. Recovery forepaw movements was observed already...
Human embryonic stem cells (hESC) and induced pluripotent (iPSC) provide new prospects for studying human neurodevelopment modeling neurological disease. In particular, iPSC-derived neural permit a direct comparison of disease-relevant molecular pathways in neurons glia derived from patients healthy individuals. A prerequisite such comparative studies are robust protocols that efficiently yield standardized populations cell types. Here we show long-term self-renewing neuroepithelial-like...
Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3ε) leads to malformations during cortical development. Here, we used patient-specific forebrain-type organoids investigate pathological changes associated with MDS. Patient-derived are significantly reduced in size, change accompanied switch from symmetric asymmetric cell division ventricular zone radial glia cells (vRGCs). Alterations microtubule...
Increasing evidence suggests that elevated Aβ42 fractions in the brain cause Alzheimer's disease (AD). Although γ-secretase modulators (GSMs), including a set of nonsteroidal anti-inflammatory drugs (NSAIDs), were found to lower various model systems, NSAID-based GSMs proved be surprisingly inefficient human clinical trials. Reasoning nonhuman and nonneuronal cells typically used pharmaceutical compound validation might not adequately reflect drug responses neurons, we pluripotent stem...
Malformations of human cortical development (MCD) can cause severe disabilities. The lack human-specific models hampers our understanding the molecular underpinnings intricate processes leading to MCD. Here, we use cerebral organoids derived from patients and genome edited-induced pluripotent stem cells address pathophysiological changes associated with a complex MCD caused by mutations in echinoderm microtubule-associated protein-like 1 (EML1) gene. EML1-deficient display ectopic neural...
Article13 September 2022Open Access Source DataTransparent process Human-specific ARHGAP11B ensures human-like basal progenitor levels in hominid cerebral organoids Jan Fischer Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden, Germany Contribution: Conceptualization, Formal analysis, Investigation, Writing - original draft Search for more papers by this author Eduardo Fernández Ortuño orcid.org/0000-0001-9414-3392 Investigation Fabio Marsoner...
Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder resulting from a functional deficiency of arylsulfatase A (ARSA), enzyme that catalyzes desulfation 3-O-sulfogalactosylceramide (sulfatide). Lack active ARSA leads to the accumulation sulfatide in oligodendrocytes, Schwann cells and some neurons triggers progressive demyelination, neuropathological hallmark MLD. Several therapeutic approaches have been explored, including replacement, autologous hematopoietic stem...
The human cortex is highly expanded and exhibits a complex structure with specific functional areas, providing higher brain function, such as cognition. Efforts to study cerebral development have been limited by the availability of model systems. Translating results from rodent studies system restricted species differences on primary tissues are hampered lack tissue well ethical concerns. Recent in pluripotent stem cell (PSC) technology include generation three-dimensional (3D)...
Apical radial glia (aRGs) are predominant progenitors during corticogenesis. Perturbing their function leads to cortical malformations, including subcortical heterotopia (SH), characterized by the presence of neurons below cortex. EML1/Eml1 mutations lead SH in patients, as well heterotopic cortex (HeCo) mutant mice. In HeCo mice, some aRGs abnormally positioned away from ventricular zone (VZ). Thus, unraveling will clarify mechanisms maintaining VZ. We pinpoint an unknown primary cilium...
Abstract The strong size increase of the human neocortex is supported both by amplification and basal translocation a neural stem cell population, radial glial cells (or bRG cells). Using live imaging second trimester fetal tissue cortical organoids, we identify two independent modes for colonization neocortex. On top an actomyosin-dependent movement called mitotic somal (MST), microtubule-dependent motion occurring during interphase, that call interphasic (IST). We show IST driven LINC...
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses protein synthesis. However, the exact molecular cellular changes induced psilocybin human brain are not known. Here, we treated cortical neurons derived from pluripotent stem cells with 5-HT2A receptor agonist psilocin - psychoactive metabolite of psilocybin. We analyzed how...
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses protein synthesis. However, the exact molecular cellular changes induced psilocybin human brain are not known. Here, we treated cortical neurons derived from pluripotent stem cells with 5-HT2A receptor agonist psilocin - psychoactive metabolite of psilocybin. We analyzed how...
Alterations in the microtubule (MT)-associated protein, tau, have emerged as a pivotal phenomenon several neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease. Although compelling lines of evidence from various experimental models suggest that hyperphosphorylation conformational changes tau can cause its aggregation into filaments, actual species effective mechanisms conspire to trigger degeneration human neurons remain obscure. Herein, we explored whether...