SyNergy: Published Datasets

Neurological diseases are on the rise – and as societies age, they affect an ever-increasing number of people, not only in Europe, but worldwide.

The Munich Cluster for Systems Neurology (SyNergy) investigates how complex neurological diseases such as Alzheimer's disease, stroke, and multiple sclerosis develop. Even though these diseases differ in their clinical manifestations, overlapping mechanisms are involved in their development. For example, the immune system gets activated in dementia, ...

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 this study, we combined single-cell multiomics with genome-wide profiling of three-dimensional nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming mediated by Neurogenin2 (Ngn2) and its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives ...

Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from gray matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single-cell RNA sequencing and spatial transcriptomics of the murine forebrain. The comparison revealed similarities but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM ...

Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer's disease. Efficient amyloid clearance has been proven in clinical trials testing anti-Aβ antibodies, by their impact on cognitive endpoints correlating with the extent of amyloid removal. However, treatment is associated with adverse side effects, such as oedema and haemorrhages, which are potentially linked to the induced immune response. To improve ...

Despite numerous studies on fetal therapy for myelomeningoceles (MMC), the pathophysiology of this malformation remains poorly understood. This study aimed to analyze the biochemical profile and proteome of amniotic fluid (AF) supernatants from MMC fetuses to explore the prenatal pathophysiology. Biochemical analysis of 61 AF samples from MMC fetuses was compared with 45 healthy fetuses' samples. Proteome analysis was conducted in 18 MMC and 18 healthy singleton fetuses, and in 5 dichorionic ...

Advancing MS-based proteomics toward clinical applications evolves around developing standardized start-to-finish and fit-for-purpose workflows for clinical specimens. Steps along the method design involve the determination and optimization of several bioanalytical parameters such as selectivity, sensitivity, accuracy, and precision. In a joint effort, eight proteomics laboratories belonging to the MSCoreSys initiative including the CLINSPECT-M, MSTARS, DIASyM, and SMART-CARE consortia performed ...

Cells were collected and lysed in urea buffer (9 M Urea, 50 mM Tris pH 8, 150 mM NaCl, 1x Roche protease inhibitor cocktail) followed by short sonification. Samples were cleared by centrifugation and protein amounts were adapted. Protein reduction was performed with dithiothreitol (DTT; 5 mM final) for 25 min at 56°C and protein alkylation by the addition of iodoacetamide (14 mM final) for 30 min at room temperature. Protein mixtures were quenched with DTT and diluted 1:5 with 1 M Tris-Hcl, pH ...

Single cell multiome (scRNA-seeq + scATAC-seq), bulk ATAC-seq, bulk RNA-seq, ChIP-seq, Cut&Run and Methyl-HiC was performed on primary mouse astrocytes (2 days post induction) transduced with doxycycline-inducible lentiviral constructs expressing either GFP, Ngn2 and PmutNgn2 respectively. Since the constructs also expressed GFP, the astrocytes were FACS sorted based on GFP expression. To profile the effect of Yy1 on direct neuronal reprogramming. scRNA-seq and bulk ATAC-seq was performed on ...

Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single cell RNA-sequencing (scRNA-seq) and spatial transcriptomics of the murine forebrain. The comparison revealed similarities, but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks ...

Astrocyte heterogeneity has been extensively studied, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. We directly compared astrocytes from cortical GM, WM, and the subependymal zone using scRNA-seq and spatial transcriptomics of murine forebrain sections. The comparison revealed significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes. Furthermore, ...

Astrocyte heterogeneity has been extensively studied, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. We directly compared astrocytes from cortical GM, WM, and the subependymal zone using scRNA-seq and spatial transcriptomics of murine forebrain sections. The comparison revealed significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes. Furthermore, ...

Anti-amyloid β-peptide (Aβ) immunotherapy was developed as treatment for Alzheimer’s disease to reduce and prevent amyloid plaque pathology and its downstream consequences. Efficient amyloid plaque clearance has been proven in clinical trials with Aducanumab, Lecanemab and Donanemab. At least two of these antibodies slow memory decline to some extent and have beneficial effects on daily living activities. The therapeutic effects correlate with the efficacy of plaque removal. However, treatment ...