Obesity-instructed TREM2-high macrophages identified by comparative analysis of diabetic mouse and human kidney at single-cell resolution [scRNA-seq: DKD_mouse]

The cross-species molecular heterogeneity from mice to patients poses grand challenges for translational research endeavors. A high-fat diet (HFD) model and a genetic model (BTBR ob/ob) at different stand points were used to generate cell atlases of diabetic and obese mise. We identified a previously unrecognized, expanding Trem2-High macrophage population in kidneys of HFD mice that modeled human TREM2-high macrophages in obese patients. Taken together, our cross-species comparison highlights shared immune and metabolic cell-state changes. Overall design: For the BTBR ob/ob genetic mouse model, we included n=5 and n=3 biological replicates for the 5- and 10-week time-point respectively for both ob/ob and wildtype strains. For the High-Fat diet (HFD) model, we combined n=4 biological replicates into a pooled “aged” group, in each of the chow and HFD conditions. The “aged” group ranged from 66 to 100 weeks old (schematic Figure 4A). For 3 biological replicates in each condition (Chow: ages 94,100; HFD: ages 83,100), there were 2 technical replicates or 10x channels run from the same cortical sample leading to a total of 7 libraries per condition.