A5045276969- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Anesthesia and Neurotoxicity Research
- RNA modifications and cancer
- Congenital heart defects research
- Growth Hormone and Insulin-like Growth Factors
- Hormonal Regulation and Hypertension
- Apelin-related biomedical research
- Barrier Structure and Function Studies
- Virus-based gene therapy research
- Planarian Biology and Electrostimulation
Helmholtz Zentrum München
2013-2024
Ludwig-Maximilians-Universität München
2013-2024
Urologische Klinik München
2021-2024
Center for Environmental Health
2022
Genomics (United Kingdom)
2022
Institute of Bioinformatics and Systems Biology
2022
Institute of Groundwater Ecology
2012
San Raffaele University of Rome
2006-2010
Vita-Salute San Raffaele University
2010
European Institute of Oncology
2008
Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use endogenous astroglia for brain repair. However, previous attempts astroglia-derived failed establish functional synapses, severe limitation neurogenesis. It remained therefore also unknown whether derived could directed distinct neuronal subtype identities by selective fate determinants....
Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 postnatal mouse astrocytes generates glutamatergic GABAergic neurons. Here, take advantage this model to study dynamics neuronal cell fate acquisition at the transcriptional level. We found and rapidly elicited distinct neurogenic programs with only a small subset shared target genes. Within subset, NeuroD4 could by...
Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the mouse hippocampus, expression SoxC transcription factors Sox4 and Sox11 is initiated around time commitment maintained immature neurons. Overexpression strongly promotes vitro neurogenesis from NSCs, whereas ablation Sox4/Sox11 prevents vivo NSCs. Moreover, demonstrate that...
Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead neurological disorders contribute the onset of age-related diseases. Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but very little is known about impact mitochondrial dysfunction on direct human cells. Here, we explore effects induced pluripotent stem cell (iPSC)-derived astrocytes carrying mutations NDUFS4 gene, important Complex I...
Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate unknown. Here, we determined comprehensive proteome of cortical astrocytes and neurons, identifying about 150 significantly enriched proteins each cell type, including transporters, metabolic enzymes, cell-type-specific antioxidants. Monitoring their transition during reprogramming revealed late...
The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models traumatic brain injury, beneficial functions proliferating reactive astrocytes outcome have been unraveled, but little is known if and when they are present in human pathology. Here we examined a broad spectrum pathologies with without intracerebral hemorrhage found striking correlation between...
Abstract Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. In study, we combined single-cell multiomics with genome-wide profiling three-dimensional nuclear architecture DNA methylation in mouse astrocyte-to-neuron mediated by Neurogenin2 (Ngn2) its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered...
Early B-cell factor 2 (EBF2) is one of four mammalian members an atypical helix-loop-helix transcription family (COE). COE proteins have been implicated in various aspects nervous and immune system development. We others generated described mice carrying a null mutation Ebf2, gene previously characterized the context Xenopus laevis primary neurogenesis neuronal differentiation. In addition to deficits neuroendocrine olfactory development, peripheral nerve maturation, Ebf2 feature ataxic gait...
Abstract Glioblastoma multiforme (GBM), the highest-grade glioma, is most frequent tumour of brain with a very poor prognosis and limited therapeutic options. Although little known about molecular mechanisms that underlie glioblastoma formation, number signal transduction routes, such as Notch Ras signalling pathways, seem to play an important role in formation GBM. In present study, we show by situ hybridization on primary material transcription factor HEY1, target pathway, specifically...
Article15 September 2022Open Access Source DataTransparent process Probing cell identity hierarchies by fate titration and collision during direct reprogramming Bob A Hersbach orcid.org/0000-0001-9995-1364 Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Oberschleißheim, Germany Division Physiological Genomics, Biomedical Munich, Ludwig-Maximilians University, Graduate School Systemic Neurosciences, Biocenter, Contribution:...
Primary aldosteronism is frequently caused by an adrenocortical aldosterone-producing adenoma (APA) carrying a somatic mutation that drives aldosterone overproduction. APAs with in KCNJ5 (APA-KCNJ5MUT) are characterized heterogeneous CYP11B2 (aldosterone synthase) expression, particular cellular composition and larger tumor diameter than those wild-type (APA-KCNJ5WT). We exploited these differences to decipher the roles of transcriptome metabolome reprogramming pathogenesis. Consecutive...
(Cell Stem Cell 28, 524–534.e1–e7, March 4, 2021) In the originally published version of our manuscript, values in Table S1 were missing a decimal separator (dot) and some columns moved due to program incompatibilities when transferring original data from .csv .xlsx. To address this, we have now added “.” corrected so that Excel file corresponds file. We apologize for oversight any resulting confusion. CRISPR-Mediated Induction Neuron-Enriched Mitochondrial Proteins Boosts Direct...