| Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting |
| Author |
Han, J; Wang, YC; Qiu, Y; Sun, DY; Liu, Y; Li, ZG; Zhou, B; Zhang, HB; Xiao, YC; Wu, GH; Ding, QR |
| Journal |
CELL DISCOVERY |
| Pub Year |
2022 |
| Type |
Article |
| Abstract |
Adipose tissue loss seen with cancer-associated cachexia (CAC) may functionally drive cachexia development. Using single-cell transcriptomics, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of white adipose tissues from patients with or without CAC. We report depot- and disease-specific clusters and developmental trajectories of adipose progenitors and immune cells. In adipose tissues with CAC, clear pro-inflammatory transitions were discovered in adipose progenitors, macrophages and CD8(+) T cells, with dramatically remodeled cell interactome among these cells, implicating a synergistic effect in promoting tissue inflammation. Remarkably, activated CD8(+) T cells contributed specifically to increased IFNG expression in adipose tissues from cachexia patients, and displayed a significant pro-catabolic effect on adipocytes in vitro; whereas macrophage depletion resulted in significantly rescued adipose catabolism and alleviated cachexia in a CAC animal model. Taken together, these results unveil causative mechanisms underlying the chronical inflammation and adipose wasting in CAC. |
| Issue |
8 |
| Volume |
8 |
