Single cell full-length transcriptome of human subcutaneous adipose tissue reveals unique and heterogeneous cell populations

White adipose tissue (WAT) is a complex mixture of adipocytes and non-adipogenic cells. Characterizing the cellular composition of WAT is critical for identifying where potential alterations occur that impact metabolism. Most single-cell (sc) RNA-Seq studies focused on the stromal vascular fraction (SVF) which does not contain adipocytes and have used technology that has a 3′ or 5′ bias. Using full-length sc/single-nuclei (sn) RNA-Seq technology, we interrogated the transcriptional composition of WAT using: snRNA-Seq of whole tissue, snRNA-Seq of isolated adipocytes, and scRNA-Seq of SVF. Whole WAT snRNA-Seq provided coverage of major cell types, identified three distinct adipocyte clusters, and was capable of tracking adipocyte differentiation with pseudotime. Compared to WAT, adipocyte snRNA-Seq was unable to match adipocyte heterogeneity. SVF scRNA-Seq provided greater resolution of non-adipogenic cells. These findings provide critical evidence for the utility of sc full-length transcriptomics in WAT and SVF in humans. [Display omitted] •Full-length sc/sc RNA-Seq provides robust gene coverage in human adipose tissue•snRNA-Seq of human adipose tissue highlights adipocyte heterogeneity•snRNA-Seq of human adipose tissue tracks adipocyte differentiation in vivo•scRNA-Seq of human SVF provides additional resolution of non-adipocyte cells Cell biology; Omics; Transcriptomics