C01 - EPO/EPOR signalling in the recovery from brain injury and disease

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 incidence of Alzheimer’s disease (AD), the leading cause of dementia, increases rapidly with age, but why age constitutes the main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths1, the latter of which is associated with secondary neuroinflammation2,3. As oligodendrocytes support axonal energy metabolism and neuronal health4,5,6,7, we hypothesized that loss of myelin integrity could be an upstream risk factor for ...

Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer’s disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APPNLGF, we demonstrate that OLs and neurons contribute to Aβ plaque burden. For rapid plaque seeding, excitatory projection neurons must provide a threshold level of Aβ. Ultimately, our findings are relevant for AD ...

This SuperSeries is composed of the SubSeries listed below.

Cortex and corpus callosum were dissected from every two animals (3-month-old) and pooled into one sample for single-nuclei RNA sequencing using 10x genomics Chromium 3’ assay. Each genotype has 2 replicates (in total n=4 animals).

Brain hemispheres were dissected from 6-month-old animals and subjected to single-nuclei RNA sequencing using 10x genomics Chromium 3’ assay. In total 4 genotypes were included for the experiment (WT, Cnp-/-, 5xFAD, Cnp-/-x5xFAD), each genotype has n=2 replicates.

Microglia cells from 6-month-old mouse brain hemispheres were isolated using the MACS sorting system and subjected to 50 bp single-end mRNA sequencing. Each genotype has n=4 replicates, in total 4 genotypes were included for experiment (WT, Cnp-/-, 5xFAD, Cnp-/-x5xFAD).

We isolated single nuclei from white matter post-mortem tissue from 5 non-neurological control samples (Ctrl) and post-mortem tissue from 4 progressive Multiple sclerosis (MS) patients. We got a total of 20 samples, which in the MS samples included different non-lesioned (normal appearing white matter) and lesioned (active lesions, chronic active lesions, chronic inactive lesions and remyelinating lesions) based on pathology, to address the cellular and functional differences between the two ...

Brain hemispheres were dissected from 6-month-old animals and subjected to single-nuclei RNA sequencing using 10x genomics Chromium 3’ assay. In total 4 genotypes were included for the experiment (WT, Cnp-/-, 5xFAD, Cnp-/-x5xFAD), each genotype has n=2 replicates.