Biology subjects

Struck, E.

Publications and source records attributed to Struck, E..

3 recordsLinked to original sources

bioRxiv2023

Temporal transcriptome analysis of the endothelial response to tumour necrosis factor

The vascular endothelium acts as a dynamic interface between blood and tissue and provides an anti-inflammatory and anti-thrombotic surface under normal conditions. Tumour necrosis factor- (TNF), a cytokine that drives acute and chronic inflammation, induces numerous transcriptional changes in endothelial cells (EC). However, the overall temporal dynamics of this response have not been fully elucidated. Here, we conducted an extended time-course analysis of the EC response to TNF, from 30 minutes to 72 hours. We identified TNF-regulated genes and used weighted gene correlation network analysis (WGCNA) to decipher co-expression profiles, uncovering two distinct temporal phases - an acute response initiated between 1-4 hours, followed by a later phase initiated between 12-24 hours. Several previously uncharacterised genes were strongly regulated during the acute phase, while the majority in the later phase were interferon-stimulated genes (ISGs). A lack of interferon transcription indicated that this TNF-induced ISG expression was independent of de novo interferon production and autocrine signalling. Furthermore, we observed two different groups of genes whose transcription was inhibited by TNF, those that resolved towards baseline levels over time, and those that did not. Our study provides insights into the global temporal dynamics of the EC transcriptional response to TNF, highlighting distinct gene expression patterns during the acute and later phases. These findings may be useful in understanding the role of EC in inflammation and developing TNF signalling-targeting therapies.

cell biology↗

bioRxiv2023

A human stomach cell type transcriptome atlas

The identification of cell type-specific genes and their modification under different conditions is central to our understanding of human health and disease. The stomach, a hollow organ in the upper gastrointestinal tract, provides an acidic environment that contributes to microbial defence and facilitates the activity of secreted digestive enzymes to process food and nutrients into chyme. In contrast to other sections of the gastrointestinal tract, detailed descriptions of cell type gene enrichment profiles in the stomach are absent from the major single cell sequencing-based atlases. Here, we use an integrative correlation analysis method to predict human stomach cell type transcriptome signatures using unfractionated stomach RNAseq data from 359 individuals. We profile parietal, chief, gastric mucous, gastric enteroendocrine, mitotic, endothelial, fibroblast, macrophage, neutrophil, T-cell and plasma cells, identifying over 1600 cell type-enriched genes. We uncover the cell type expression profile of several non-coding genes strongly associated with the progression of gastric cancer and, using a sex-based subset analysis, uncover a panel of male-only chief cell-enriched genes. This study provides a roadmap to further understand human stomach biology.

systems biology↗

bioRxiv2023

A tissue centric atlas of cell type transcriptome enrichment signatures

Genes with cell type specific expression typically encode for proteins that have cell type specific functions. Single cell RNAseq (scRNAseq) has facilitated the identification of such genes, but various challenges limit the analysis of certain cell types and lowly expressed genes. Here, we performed an integrative network analysis of over 6000 bulk RNAseq datasets from 15 human organs, to generate a tissue-by-tissue cell type enrichment prediction atlas for all protein coding genes. We profile all the major constituent cell types, including several that are fragile or difficult to process and thus absent from existing scRNAseq-based atlases. The stability and read depth of bulk RNAseq data, and the high number of biological replicates analysed, allowed us to identify lowly expressed cell type enriched genes that are difficult to classify using existing methods. We identify co-enriched gene panels shared by pancreatic alpha and beta cells, chart temporal changes in cell enrichment signatures during spermatogenesis, and reveal that cells in the hair root are a major source of skin enriched genes. In a cross-tissue analysis, we identify shared gene enrichment signatures between highly metabolic and motile cell types, and core identity profiles of cell types found in across tissue types. Our study provides the only cell type gene enrichment atlas generated independently of scRNAseq, representing a new addition to our existing toolbox of resources for the understanding of gene expression across human tissues.

systems biology↗