Single-cell transcriptomics of East-Asian pancreatic islets cells

• Published in: Scientific reports Vol. 7; no. 1; pp. 5024 - 8
• Main Authors: Dorajoo, Rajkumar, Ali, Yusuf, Tay, Vanessa S. Y., Kang, Jonathan, Samydurai, Sudhagar, Liu, Jianjun, Boehm, Bernhard O.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38/39; 38/91; 631/337/2019; 631/337/572; Cell death; Cell lineage; Diabetes mellitus; Gene expression; Humanities and Social Sciences; Islets of Langerhans; multidisciplinary; Pancreas; Ribonucleic acid; RNA; Rodents; Science; Science (multidisciplinary); TOR protein; Tryptophan; Ubiquitination; Variance analysis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-05266-4

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.