Exploration of Conserved Human Adipose Subpopulations Using Targeted Single-Nuclei RNA Sequencing Data Sets.

Abstract

Background: Smooth-muscle cells and pericytes are mural cells. Pericytes can differentiate into myofibroblasts, chondrocytes, vascular smooth-muscle cells, and adipocytes, marking them as a distinct progenitor population. Our goal was to molecularly define the progenitor cell populations in human adipose tissues and test the adipogenic potential of human mural cells.

Methods: We used informatic analysis of single-cell RNA sequencing data from human tissues to identify and define pericytes and adipose progenitor cells found in human adipose tissues, including perivascular, brown, and white adipose tissues.

Results: We established tissue-specific patterns of gene expression in pericytes and other putative human adipocyte progenitor cells. PPARG-expressing pericytes were present in multiple human adipose depots with consistent expression of COL25A1, MYO1B, and POSTN. We also found evidence of tissue-specific pericyte markers. Although there is some conservation between human and mouse adipose tissues, human pericyte populations have unique, depot-specific gene expression signatures. Immunofluorescence staining of human adipose tissue revealed the presence of pericytes both distant from and adjacent to vasculature in human adipose tissue. Additionally, we demonstrated the potential of human brain pericytes and aortic vascular smooth-muscle cells to differentiate into adipocytes in vitro on the basis of intracellular lipid accumulation and expression of adipocyte markers.

Conclusions: Human adipose cell populations are distinct from mice, and the pericyte subpopulation in human adipose tissues are present across adipose depots. Given that vascular mural cells, including pericytes and smooth-muscle cells, can undergo adipogenesis, we postulate that they are a novel source of adipocytes in the vascular microenvironment.