ArticleDiabetologia2018
Patterns of differential gene expression in a cellular model of human islet development, and relationship to type 2 diabetes predisposition.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
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- Electrophysiological characterisation of iPSC-derived human β-like cells and anbioRxiv : the preprint server for biology · 2023Article
- Nanopore Sequencing ofACS omega · 2023Article
- Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression.Diabetologia · 2023Article
- Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in β-cell subpopulations associated with glycemic control.BMC genomics · 2023Article
- Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases.Advances in experimental medicine and biology · 2023Article
- Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.Nature metabolism · 2020Article
- Molecular and genetic regulation of pig pancreatic islet cell development.Development (Cambridge, England) · 2020Article
- Article
- Analysis of Differentiation Protocols Defines a Common Pancreatic Progenitor Molecular Signature and Guides Refinement of Endocrine Differentiation.Stem cell reports · 2020Article
- Loss of ZnT8 function protects against diabetes by enhanced insulin secretion.Nature genetics · 2019Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
aims/hypothesisMost type 2 diabetes-associated genetic variants identified via genome-wide association studies (GWASs) appear to act via the pancreatic islet. Observed defects in insulin secretion could result from an impact of these variants on islet development and/or the function of mature islets. Most functional studies have focused on the latter, given limitations regarding access to human fetal islet tissue. Capitalising upon advances in in vitro differentiation, we characterised the transcriptomes of human induced pluripotent stem cell (iPSC) lines differentiated along the pancreatic endocrine lineage, and explored the contribution of altered islet development to the pathogenesis of type 2 diabetes.
methodsWe performed whole-transcriptome RNA sequencing of human iPSC lines from three independent donors, at baseline and at seven subsequent stages during in vitro islet differentiation. Differentially expressed genes (q < 0.01, log
resultsWe identified 9409 differentially expressed genes across all stages, including many known markers of islet development. Integration of differential expression data with information on transcription factor motifs highlighted the potential contribution of REST to islet development. Over 70% of genes mapping within type 2 diabetes-associated credible intervals showed peak differential expression during islet development, and type 2 diabetes GWAS loci of largest effect (including TCF7L2; log CONCLUSIONS/
interpretationThe present study characterises RNA expression profiles during human islet differentiation, identifies potential transcriptional regulators of the differentiation process, and suggests that the inherited predisposition to type 2 diabetes is partly mediated through modulation of islet development. DATA AVAILABILITY: Sequence data for this study has been deposited at the European Genome-phenome Archive (EGA), under accession number EGAS00001002721.
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