Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting.
Jun HanYuchen WangYan QiuDiya SunYan LiuZhigang LiBen ZhouHaibing ZhangYi-Chuan XiaoGuohao WuQiurong DingPublished in: Cell discovery (2022)
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.
Keyphrases
- adipose tissue
- single cell
- insulin resistance
- rna seq
- high fat diet
- oxidative stress
- gene expression
- high throughput
- induced apoptosis
- type diabetes
- newly diagnosed
- poor prognosis
- metabolic syndrome
- ejection fraction
- cell proliferation
- cell death
- mesenchymal stem cells
- signaling pathway
- long non coding rna
- prognostic factors
- anti inflammatory