Depot-Specific Differences and heterogeneity of Adipose-Derived Stem Cells in Diet-Induced Obesity

Obesity is a global health concern. Studying the heterogeneity of ADSCs play pivotal roles in understanding metabolic disorders such as obesity. Using Mass cytometry, we discerned the spatial heterogeneity of ADSCs and their alterations at the single cell level in a diet-induced-obesity (DIO) model treated with Liraglutide. We characterized the relationship of ADSCs markers and found that CD26 and CD142 are capable of identifying the most representative heterogeneous ADSCs in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT). Specifically, CD26+CD142- and CD26+CD142+ADSCs were exclusive to SAT and VAT, respectively, while CD26-CD142+ADSCs were present in both. To acquire more robust examination of the expression variances for a range of functional markers within these depot-specific heterogeneous subpopulations, transcriptomic sequencing was performed on the Fluorescence-activated cell sorting (FACS) sorted CD26+CD142-, CD26+CD142+ and CD26-CD142+ ADSCs from SAT and VAT of chow diet mice. In the VAT of DIO mice, we observed significant down-regulation of CD26+CD142+ ADSCs and up-regulation of CD26-CD142+ ADSCs, both of which could be mitigated by Liraglutide. Our research illuminates the spatial heterogeneity of ADSCs and their alterations under DIO, which can be potentially reversed by Liraglutide treatment. This study contributes new insights for identifying more specific ADSCs subgroups to explore the etiology for metabolic-related diseases. Overall design: FACS was performed on SVFs from SAT and VAT of 30 chow diet mice (12-14 weeks old) to obtain ADSCs subclusters with different expression pattern of CD26 and CD142. A total of 5 samples were obtained from FACS sorting, which included a single sample for SAT_CD142+, SAT_CD26+CD142-, VAT_CD26+CD142+ ADSCs, and two samples for VAT_CD142+ ADSCs. Transcriptomic sequencing was performed on these FACS sorted ADSCs subpopulations.