Genome engineering of a neuronal specific, optogenetic, induced pluripotent stem cell line.

Control of neuronal activity by optogenetic tools is increasingly explored in disease modelling and optogenetics and holds great promise for regenerative therapy. To investigate neuronal connectivity with other excitable cells we established an optogenetic induced pluripotent stem cell line. The SynfChrimson line harbors a stably integrated, fast, red light-activatable channel (f-Chrimson), under the control of synapsin promotor in the AAVS1 locus.

Generation of a fluorescent oligodendrocyte reporter line in human induced pluripotent stem cells.

Human brain organoids can serve as models to study myelination, a process orchestrated by oligodendrocytes. Real-time imaging provides new insights on the communication of oligodendrocytes with neurons as well as demyelination processes in patient derived organoids. PLP1, a prominent myelin protein within the central nervous system, is associated with demyelinating diseases, such as Pelizaeus-Merzbacher.

Generation of Pelizaeus-Merzbacher disease (PMD) mutant (PLP1-C33Y) in induced pluripotent stem cell (iPSC) by CRISPR/Cas9 genome editing.

Genetic alterations in the PLP1 gene, i.e. point mutations and duplications, are associated with demyelinating disease Pelizaeus-Merzbacher.

Understanding and treating paediatric hearing impairment.

Sensorineural hearing impairment is the most frequent form of hearing impairment affecting 1-2 in 1000 newborns and another 1 in 1000 adolescents. More than 50% of congenital hearing impairment is of genetic origin and some forms of monogenic deafness are likely targets for future gene therapy. Good progress has been made in clinical phenotyping, genetic diagnostics, and counselling.

Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control.

Aims: Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias.

Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids.

Brain organoids are promising tools for disease modeling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here, we report the directed self-organization of human induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network at a macroscale tissue format.

Atrial fibrillation and heart failure-associated remodeling of two-pore-domain potassium (K) channels in murine disease models: focus on TASK-1.

Understanding molecular mechanisms involved in atrial tissue remodeling and arrhythmogenesis in atrial fibrillation (AF) is essential for developing specific therapeutic approaches. Two-pore-domain potassium (K) channels modulate cellular excitability, and TASK-1 (K3.1) currents were recently shown to alter atrial action potential duration in AF and heart failure (HF).

Stretch-activated two-pore-domain (K) potassium channels in the heart: Focus on atrial fibrillation and heart failure.

Two-pore-domain potassium (K) channels modulate cellular excitability. The significance of stretch-activated cardiac K channels (K2.1, TREK-1, KCNK2; K4.

Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury.

Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry.