Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 hours.
Caleb M GrenkoLori L BonnycastleHenry J TaylorTingfen YanAmy J SwiftCatherine C RobertsonNarisu NarisuMichael R ErdosFrancis S CollinsD Leland TaylorPublished in: bioRxiv : the preprint server for biology (2023)
Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycemia, beta cell glucotoxicity, and ultimately type 2 diabetes (T2D). In this study, we sought to explore the effects of hyperglycemia on human pancreatic islet (HPI) gene expression by exposing HPIs from two donors to low (2.8mM) and high (15.0mM) glucose concentrations over 24 hours, assaying the transcriptome at seven time points using single-cell RNA sequencing (scRNA-seq). We modeled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Across all cell types, we identified 1,528 genes associated with time, 1,185 genes associated with glucose exposure, and 845 genes associated with interaction effects between time and glucose. We clustered differentially expressed genes across cell types and found 347 modules of genes with similar expression patterns across time and glucose conditions, including two beta cell modules enriched in genes associated with T2D. Finally, by integrating genomic features from this study and genetic summary statistics for T2D and related traits, we nominate 374 candidate effector genes that may underlie genetic associations for T2D and related traits.
Keyphrases
- single cell
- rna seq
- genome wide
- blood glucose
- high throughput
- gene expression
- type diabetes
- dna methylation
- endothelial cells
- cell therapy
- genome wide identification
- cardiovascular disease
- poor prognosis
- stem cells
- insulin resistance
- cross sectional
- dendritic cells
- cancer therapy
- induced pluripotent stem cells
- blood pressure
- long non coding rna
- skeletal muscle
- type iii