A single-cell transcriptomic atlas of primate pancreatic islet aging.
Jingyi LiYuxuan ZhengPengze YanMoshi SongSi WangLiang SunZunpeng LiuShuai MaJuan Carlos Izpisua BelmontePiu ChanQi ZhouWeiqi ZhangGuang-Hui LiuFuchou TangJing QuPublished in: National science review (2020)
Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes. Endocrine cells age heterogeneously, complicating the efforts to unravel the molecular drivers underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased transcriptional variations, aged β-cells showed increased unfolded protein response (UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways, comprising adaptive UPR during pancreatic aging. Notably, we found aging-related β-cell-specific upregulation of HSP90B1, an endoplasmic reticulum-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue to delaying β-cell aging and preventing aging-related diabetes.
Keyphrases
- single cell
- rna seq
- induced apoptosis
- endoplasmic reticulum stress
- cell cycle arrest
- high glucose
- high throughput
- type diabetes
- signaling pathway
- cardiovascular disease
- gene expression
- oxidative stress
- cell therapy
- adipose tissue
- stem cells
- single molecule
- drug induced
- mesenchymal stem cells
- poor prognosis
- metabolic syndrome
- long non coding rna
- skeletal muscle
- insulin resistance
- pi k akt
- quality improvement
- heat stress
- heat shock protein