Rajkumar Dorajoo, Yusuf Ali, Vanessa S Y Tay, Jonathan Kang, Sudhagar Samydurai, Jianjun Liu, Bernhard O Boehm
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.
Cell Metab. 2016 Oct 11;24(4):593-607
[PMID:
27667667]
Mol Neurobiol. 2013 Oct;48(2):294-301
[PMID:
23813101]
Cell Metab. 2016 Oct 11;24(4):608-615
[PMID:
27667665]
Lancet Diabetes Endocrinol. 2016 Jan;4(1):2-3
[PMID:
26577717]
Am J Hum Genet. 2014 Dec 4;95(6):689-97
[PMID:
25466870]
Autophagy. 2014 Jun;10 (6):1004-14
[PMID:
24879150]
Curr Diab Rep. 2012 Dec;12(6):686-96
[PMID:
22993124]
Nat Rev Endocrinol. 2013 Sep;9(9):537-47
[PMID:
23712250]
Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):3293-8
[PMID:
26951663]
Diabetes. 2016 Dec;65(12 ):3794-3804
[PMID:
27625022]
J Proteomics. 2015 Mar 18;117:156-67
[PMID:
25638021]
Br J Nutr. 2009 Feb;101(4):465-73
[PMID:
18842159]
Lancet Diabetes Endocrinol. 2014 Dec;2(12):935-43
[PMID:
25081582]
PLoS One. 2016 Sep 16;11(9):e0163046
[PMID:
27636901]
Diabetes. 2016 Dec;65(12 ):3610-3620
[PMID:
27702832]
Diabetologia. 2015 Oct;58(10):2218-28
[PMID:
26215305]
Nat Rev Endocrinol. 2016 May;12 (5):263-73
[PMID:
27020257]
Diabetes. 2016 Oct;65(10 ):3028-38
[PMID:
27364731]
EMBO Rep. 2016 Feb;17 (2):178-87
[PMID:
26691212]
Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3038-43
[PMID:
24516164]