Biology subjects

Woodbury, M.

Publications and source records attributed to Woodbury, M..

3 recordsLinked to original sources

bioRxiv2021

Extracellular Hsp90α Detoxifies β-Amyloid Fibrils Through an NRF2 and Autophagy Dependent Pathway

We have investigated the role of extracellular Heat shock protein 90 alpha (eHsp90) in conferring protection of neuronal cells against fibrillary amyloid beta (f-A{beta}1-42) toxicity mediated by microglial cells. Formation of f-A{beta}1-42 plaques leads to neurotoxic inflammation, a critical pathological feature of Alzheimers Disease. We observed increased uptake and clearance of internalized f-A{beta}1-42 by microglial cells treated with eHsp90, an effect associated with activation of NRF2 (NF-E2-related factor 2) - mediated autophagy. eHsp90 thus mitigated the neuronal toxicity of f-A{beta}1-42-activated microglia. In addition, eHsp90 facilitated f-A{beta}1-42 engulfment by microglial cells in vitro. In summary, eHsp90 triggers NRF2-mediated autophagy in microglia and thus protects against the neurotoxic effects of f-A{beta}1-42.

cell biology↗

bioRxiv2020

ABACUS: A flexible UMI counter that leverages intronic reads for single-nucleus RNAseq analysis

Single-nucleus RNA sequencing (sNuc-RNAseq) is an emerging powerful genomics technology that combines droplet microfluidics with next-generation sequencing to interrogate transcriptome changes at single nucleus resolution. Here we developed Abacus, a flexible UMI counter software for sNuc-RNAseq analysis. Abacus draws extra information from sequencing reads mapped to introns of pre-mRNAs (~60% of total data) that are ignored by many single-cell RNAseq analysis pipelines. When applied to our pilot human brain sNuc-RNAseq data, ABACUS nearly doubled the number of nuclei identified by the CellRanger workflow, recovering a large number of nuclei from non-neuronal cells. By incorporating intronic reads into gene expression quantification, we showed that they encoded additional and valid transcription features of individual cells and could be used to improve cluster resolution of different cell types. By separately counting UMIs derived from forward and reverse intronic reads and from exonic reads, Abacus gives users flexibility in representing genes expressed at different abundance levels. In summary, Abacus represents a flexible, improved workflow for sNuc-RNAseq data processing and analysis.

bioinformatics↗

bioRxiv2020

Profiling microglia from AD donors and non-demented elderly in acute human post-mortem cortical tissue

Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimers disease. Here, we investigated microglia transcriptomes at bulk and single cell level in non-demented elderly and AD donors using acute human post-mortem cortical brain samples. We identified 9 human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing.

neuroscience↗