Single-cell transcriptomics of East-Asian pancreatic islets cells.

ABSTRACT: Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on ?- and ?-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between ?- and ?-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 ?, 105 ?, 6 ? endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between ?- and ?-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian ?-cells. We report on East-Asian ?- and ?-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian ?-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis.

SUBMITTER: Dorajoo R 

PROVIDER: S-EPMC5504042 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature