Christine Stadelmann-Nessler

https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

The Z01 Bioimaging and Tissue Analysis Platform supports various CRC projects by analyzing human tissue samples and using state-of-the-art correlative light and electron microscopy techniques to study CNS recovery at a detailed level. During the first funding period, Z01 contributed to understanding key aspects of CNS recovery, such as axon damage, inflammation’s role in tissue healing, and how certain cells help repair nerve fibers. In the next funding phase, our focus will be on two main goals: ...

In autoantibody-mediated gliopathies, such as Neuromyelitis Optica Spectrum Disorder, pathology often spreads quickly beyond the intital target cell type to affect other glial cells. In this project, we will identify glial-glia interactions that act either as checkpoints of acute pathology spread or as checkpoints of lesion repair. To achieve this, we will use in vivo imaging in animal models, as well as genetic interventions and close correlation with human neuropathology, to study how the ...

The cerebral cortex contains a special, perineuronally localized population of oligodendrocyte lineage cells with possible functions in connectivity and myelination. We hypothesize that this cell population serves as a reservoir of remyelinating cells after myelin damage. We will apply spatial transcriptome analysis with subcellular resolution in experimental models of demyelination and human tissue from patients with multiple sclerosis to define physiological and pathological states of perineuronal ...

As tissue-resident macrophages of the central nervous system parenchyma, microglia perform diverse essential functions during homeostasis and perturbations1. They primarily interact with neurons by means of synaptic engulfment and through the rapid elimination of apoptotic cells and non-functional synapses2. Here, by combining unbiased lipidomics and high-resolution spatial lipid imaging, deep single-cell transcriptome analysis and novel cell-type-specific mutants, we identified a previously ...

Single-cell studies have revealed substantial microglial diversity in development, homeostasis and disease. However, a framework enabling comparison and stratification of microglial states across contexts is needed. Here we generated an atlas of myeloid cell states by single-cell RNA sequencing more than one million central nervous system cells from more than 30 physiological and pathological conditions. This atlas enables us to establish a comprehensive taxonomy of myeloid cell states across ...

Compartmentalized inflammation is a key driver of multiple sclerosis (MS) progression, but the mechanisms sustaining its persistence remain unclear. A hallmark of this persistent and slowly evolving inflammatory process is chronic active MS lesions. We generated a high-resolution, single-cell molecular and spatial atlas of such lesions by combining single-nucleus RNA sequencing (snRNA-seq) with multiplexed error-robust fluorescence in situ hybridization (MERFISH). Within lesion rims, we identified ...

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB–dependent activation in phagocytes occurs rapidly after myelin injury. We found ...

Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer's disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer's disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against ...