Single-cell transcriptomics of East-Asian pancreatic islets cells

Abstract

Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on α- and β-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 α- and β-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 α, 105 β, 6 δ endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between α- and β-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 β-cells. We report on East-Asian α- and β-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian β-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis.

Figure 1

Representative immunofluorescence staining showing co-localization of transcripts with INS + cells and not GCG + cells from pancreas of three different subjects. Subject 1 (A,D and G), subject 2 (B,E and H) and subject 3 (C,F and I). (A,B and C) shows DNAJC3 (green), INS (red), GCG (blue) and nucleus (grey) stains. (D,E and F) shows PFKB2 (green), INS (red), GCG (blue) and nucleus (grey) stains. (G,H and I) shows UCHL1 (green), INS (red) and nucleus (grey) stains. Cell co-expressing INS and DNAJC or PFKB2 or UCHL1 are represented as yellow. Inserts show cells expressing insulin (red) and the respective gene of interest (green) at higher magnification and at individual channels. Scale bar represents 20 µm.