A human adipose tissue cell-type transcriptome atlas.

The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) datasets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.