A5011283122- Pluripotent Stem Cells Research
- Parkinson's Disease Mechanisms and Treatments
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Nuclear Receptors and Signaling
- Metabolism and Genetic Disorders
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Pharmacological Effects and Toxicity Studies
- Genetic Neurodegenerative Diseases
- Epilepsy research and treatment
- Gut microbiota and health
- Urinary Bladder and Prostate Research
- Genetics and Neurodevelopmental Disorders
- 3D Printing in Biomedical Research
- Neurogenesis and neuroplasticity mechanisms
- Probiotics and Fermented Foods
- Alzheimer's disease research and treatments
- Human Health and Disease
- Antimicrobial Peptides and Activities
Novo Nordisk Foundation
2021-2024
University of Copenhagen
2021-2024
University of Luxembourg
2017-2023
Evangelisches Krankenhaus Oberhausen
2017
Kiel University
2013
European Neuroscience Institute Göttingen
2011
Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate complexity brain. Here, we describe a robust organoid system highly specific to midbrain derived from regionally patterned neuroepithelial stem cells. These organoids contain spatially organized groups dopaminergic neurons, which make them an attractive model for study Parkinson's disease. Midbrain are characterized detail neuronal, astroglial,...
Dysregulation of histone acetylation has been implicated in the onset age-associated memory impairment and pathogenesis neurodegenerative diseases. Elevation via administration deacetylase (HDAC) inhibitors is currently being pursued as a novel therapeuti c avenue to treat linked Alzheimer's disease (AD). Here we show that severe amyloid pathology correlates with pronounced dysregulation forebrain APPPS1-21 mice. Importantly, prolonged treatment pan-HDAC inhibitor sodium butyrate improved...
Significance Animals form functional unities with communities of microbes. Often, these bacterial are highly specific to host species and resemble phylogeny. But which factors determine community membership? Which host-factors capable selecting suitable bacteria by inhibiting colonization potential foreign colonizers? In this study, we show that animals express a species-specific repertoire antimicrobial peptides, supports maintains community. Loss-of-function experiments showed peptide...
Abstract Parkinson's disease (PD)‐specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient‐specific derived from induced pluripotent stem cells carrying the LRRK2‐G2019S mutation, is optimized 3D microfluidics. automated image analysis algorithms are implemented to enable pharmacophenomics disease‐relevant conditions. In contrast this approach reveals robust High‐content imaging data show decreased dopaminergic differentiation...
The etiology of Parkinson's disease (PD) is only partially understood despite the fact that environmental causes, risk factors, and specific gene mutations are contributors to disease. Biallelic in phosphatase tensin homolog (PTEN)-induced putative kinase 1 (PINK1) involved mitochondrial homeostasis, vesicle trafficking, autophagy sufficient cause PD.We sought evaluate difference between controls' PINK1 patients' derived neurons their transition from neuroepithelial stem cells neurons,...
Abstract Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis -regulatory elements, predicting enhancer strength and identifying their target genes is challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature H2BNTac prominently marks candidate subset promoters discriminates them ubiquitously promoters. Two mechanisms underlie the distinct specificity: (1) unlike...
Genome editing and human induced pluripotent stem cells hold great promise for the development of isogenic disease models correction disease-associated mutations tissue therapy. CRISPR-Cas9 has emerged as a versatile simple tool engineering such purposes. However, current protocols to derive genome-edited lines require screening number clones obtain one free random integration or on-locus non-homologous end joining (NHEJ)-containing alleles. Here, we describe an efficient method biallelic...
The p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) has been identified as most prevalent genetic cause familial and sporadic Parkinson's disease (PD). Cre-LoxP recombination system used to correct LRRK2-G2019S in patient derived human induced pluripotent stem cells (hiPSCs) order generate isogenic controls. However, remaining LoxP site can influence gene expression. In this study, we report generation a footprint-free hiPS cell line edited with CRISPR/Cas9 piggyBac...
In all eukaryotes, acetylation of histone lysine residues correlates with transcription activation. Whether is a cause or consequence debated. One model suggests that promotes the recruitment and/or activation acetyltransferases, and occurs as ongoing transcription. However, extent to which shapes global protein landscapes not known. Here, we show remains virtually unaltered after acute inhibition. Transcription inhibition ablates co-transcriptionally occurring ubiquitylation H2BK120 but...
Abstract Mitochondrial Rho GTPase 1 (Miro1) protein is a well-known adaptor for mitochondrial transport and also regulates quality control function. Furthermore, Miro1 was associated with mitochondrial-endoplasmic reticulum (ER) contact sites (MERCs), which are key regulators of cellular calcium homeostasis the initiation autophagy. Impairments these mechanisms were linked to neurodegeneration in Parkinson’s disease (PD). We recently revealed that PD fibroblasts harboring mutations displayed...
In briefWalter et al. show that differentiating iPSC-derived neurons carrying the LRRK2-G2019 mutation are characterized by faster initial neuronal differentiation and cell-cycle exit, as well increased cell death, compared to controls.Downregulation of transcription factor NR2F1 appears key mediate LRRK2-G2019S-dependent phenotypes.
Abstract Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis-regulatory elements, predicting enhancer strength, and identifying their target genes remains challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a genuine signature H2BNTac prominently marks candidate promoters discriminates them ubiquitously promoters. Two mechanisms afford the distinct specificity. (1) Unlike...
Abstract Autophagic processes play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple and distinct steps pathway. Current analyses tools do not deliver required detail for dissecting pathway intermediates. The development new to analyze autophagic qualitatively quantitatively more straightforward manner is required. Defining all intermediates high-throughput technologically challenging has been addressed yet. Here, we...
Parkinson's disease (PD) is a multifactorial disorder with complex etiology. The most prevalent PD associated mutation, LRRK2-G2019S linked to familial and sporadic cases. Based on the multitude of genetic predispositions in incomplete penetrance LRRK2-G2019S, we hypothesize that modifiers patients' background act as susceptibility factors for developing PD. To assess modifiers, used human induced pluripotent stem cell-derived neuroepithelial cells (NESCs). Isogenic controls distinguish...
Abstract The etiology of Parkinson’s disease (PD) is only partially understood despite the fact that environmental causes, risk factors, and specific gene mutations are contributors to disease. Biallelic in PTEN-induced putative kinase 1 ( PINK1 ) involved mitochondrial homeostasis, vesicle trafficking, autophagy, sufficient cause PD. By comparing PD patient-derived cells, we show differences their energetic profile, imbalanced proliferation, apoptosis, mitophagy, a reduced differentiation...
Fibroblasts from two Parkinson's disease (PD) patients carrying either the heterozygous mutation c.815G > A (Miro1 p.R272Q) or c.1348C T p.R450C) in RHOT1 gene, were converted into induced pluripotent stem cells (iPSCs) using RNA-based and episomal reprogramming, respectively. The corresponding isogenic gene-corrected lines have been generated CRISPR/Cas9 technology. These pairs will be used to study Miro1-related molecular mechanisms underlying neurodegeneration relevant iPSC-derived...
Background: The workup of the etiology autism (metabolism, genetics, imaging) usually gains no or only few helpful findings. Therefore, these investigations are often not performed until late at all.
Abstract Autophagy and mitophagy play a central role in cellular homeostasis. In pathological conditions, the flow of autophagy can be affected at multiple distinct steps pathways. Unfortunately, level detail current state art analyses does not allow detection or dissection pathway intermediates. Moreover, is conducted low-throughput manner on bulk cell populations. Defining intermediates high-throughput technologically challenging, has been addressed so far. Here, we overcome those...