Isabel Reinisch, Adhideb Ghosh, Falko Noé, Wenfei Sun, Hua Dong, Peter Leary, Arne Dietrich, Anne Hoffmann, Matthias Blüher, Christian Wolfrum
This respository contains code and files related to our study: Unveiling adipose populations linked to metabolic health in obesity. Cell Metabolism.
Precision medicine is still not considered as a standard of care in obesity treatment, despite a large heterogeneity in the metabolic phenotype of individuals with obesity. One of the strongest factors influencing the variability in metabolic disease risk is adipose tissue (AT) dysfunction; however, there is little understanding of the link between distinct cell populations, cell-type-specific transcriptional programs, and disease severity. Here, we generated a comprehensive cellular map of subcutaneous and visceral AT of individuals with metabolically healthy and unhealthy obesity. By combining single-nucleus RNA-sequencing data with bulk transcriptomics and clinical parameters, we identified that mesothelial cells, adipocytes, and adipocyte-progenitor cells exhibit the strongest correlation with metabolic disease. Furthermore, we uncovered cell-specific transcriptional programs, such as the transitioning of mesothelial cells to a mesenchymal phenotype, that are involved in uncoupling obesity from metabolic disease. Together, these findings provide valuable insights by revealing biological drivers of clinical endpoints.
App to explore correlations between bulk gene expression and clinical parameters
App to explore snRNAseq data from subcutaneous AT
App to explore snRNAseq data from visceral AT
DEGs
: Contains tissue and cell type specific DEGs for subcutaneous / visceral ATMarkerGenes
: Contains cell type and subpopulation specific top marker genes for subcutaneous / visceral ATSNPdemux
: Contains code to run SNP demultiplexing using cellSNP and vireoRscripts
: Contains scripts used to analyze databulkRNA
: DE analysis, Bisque deconvolution, Clinical correlationssnRNA
: Pre-processing, Sample integration, Multi-cellular factor analysis, Cell type re-clustering
For questions regarding data analysis, please write to adhideb.ghosh[AT]hest.ethz.ch.
For questions regarding web applications, please write to falnoe[AT]ethz.ch.
Corresponding authors: Matthias Blüher (matthias.blueher[AT]medizin.uni-leipzig.de) and Christian Wolfrum (christian-wolfrum[AT]ethz.ch).