ArticlePloS one2013
Novel pancreatic endocrine maturation pathways identified by genomic profiling and causal reasoning.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 15 citations in OpenAlex.
- Demixing and Analysis of Complex Biological Raman Hyperspectra Based on Peak Fitting, Amplitude Trend Clustering, and Spectrum Reconstruction.Applied spectroscopy · 2025Article
- Causal Inference Engine: a platform for directional gene set enrichment analysis and inference of active transcriptional regulators.Nucleic acids research · 2019Article
- Interpreting transcriptional changes using causal graphs: new methods and their practical utility on public networks.BMC bioinformatics · 2016Article
- Endothelial cells mediate islet-specific maturation of human embryonic stem cell-derived pancreatic progenitor cells.Tissue engineering. Part A · 2015Article
- Profiling of embryonic stem cell differentiation.The review of diabetic studies : RDS · 2014Review
- Molecular causes of transcriptional response: a Bayesian prior knowledge approach.Bioinformatics (Oxford, England) · 2013Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have used a previously unavailable model of pancreatic development, derived in vitro from human embryonic stem cells, to capture a time-course of gene, miRNA and histone modification levels in pancreatic endocrine cells. We investigated whether it is possible to better understand, and hence control, the biological pathways leading to pancreatic endocrine formation by analysing this information and combining it with the available scientific literature to generate models using a casual reasoning approach. We show that the embryonic stem cell differentiation protocol is highly reproducible in producing endocrine precursor cells and generates cells that recapitulate many aspects of human embryonic pancreas development, including maturation into functional endocrine cells when transplanted into recipient animals. The availability of whole genome gene and miRNA expression data from the early stages of human pancreatic development will be of great benefit to those in the fields of developmental biology and diabetes research. Our causal reasoning algorithm suggested the involvement of novel gene networks, such as NEUROG3/E2F1/KDM5B and SOCS3/STAT3/IL-6, in endocrine cell development We experimentally investigated the role of the top-ranked prediction by showing that addition of exogenous IL-6 could affect the expression of the endocrine progenitor genes NEUROG3 and NKX2.2.
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Registered trials
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