ArticleDifferentiation; research in biological diversity2009
Developmental pathways during in vitro progression of human islet neogenesis.
Article in Differentiation; research in biological diversity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed.
- Directed differentiation of pancreatic δ cells from human pluripotent stem cells.Nature communications · 2024Article
- NF-κB activity during pancreas development regulates adult β-cell mass by modulating neonatal β-cell proliferation and apoptosis.Cell death discovery · 2021Article
- The Genetic Contribution to Type 1 Diabetes.Current diabetes reports · 2019Review
- Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort.Journal of autoimmunity · 2018Article
- Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic.Stem cell reports · 2018Article
- 17Journal of the Endocrine Society · 2017Article
- Effect of Wnt Signaling on the Differentiation of IsletBioMed research international · 2017Article
- β-cell insulin receptor deficiency during in utero development induces an islet compensatory overgrowth response.Oncotarget · 2016Article
- Potential Factors for the Differentiation of ESCs/iPSCs Into Insulin-Producing Cells.Cell medicine · 2015Article
- The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus.Regulatory peptides · 2013Article
- A Small Molecule Swertisin from Enicostemma littorale Differentiates NIH3T3 Cells into Islet-Like Clusters and Restores Normoglycemia upon Transplantation in Diabetic Balb/c Mice.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Ubiquitin C-terminal hydrolase L1 is required for pancreatic beta cell survival and function in lipotoxic conditions.Diabetologia · 2012Article
- Gene expression profiles of Beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes.PloS one · 2010Article
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4 authors.
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Abstract
Islet neogenesis, or the differentiation of islet cells from precursor cells, is seen in vitro and in vivo both embryonically and after birth. However, little is known about the differentiation pathways during embryonic development for human pancreas. Our previously reported in vitro generation of islets from human pancreatic tissue provides a unique system to identify potential markers of neogenesis and to determine the molecular mechanisms underlying this process. To this end, we analyzed the gene expression profiles of three different stages during in vitro islet generation: the Initially Adherent, Expanded, and Differentiated stages. Samples from four human pancreases were hybridized to Affymetrix U95A GeneChips, and data analyzed using GeneSpring 7.0/9.0 software. Using scatter plots we selected genes with a 2-fold or greater differential expression. Of the 12,000 genes/ESTs present on these arrays, 295 genes including 38 acinar-enriched genes were selectively lost during the progression from the Initially Adherent stage to the Expanded stage; 468 genes were increased in this progression to Expanded tissue; and 529 genes had a two-fold greater expression in the Differentiated stage than in the Expanded tissue. Besides the expected increases in insulin, glucagon, and duct markers (mucin 6, aquaporin 1 and 5), the beta cell auto-antigen IA-2/phogrin was increased 5-fold in Differentiated. In addition, developmentally important pathways, including notch/jagged, Wnt/frizzled, TGFbeta superfamily (follistatin, BMPs, and SMADs), and retinoic acid (COUP-TFI, CRABP1, 2, and RAIG1) were differentially regulated during the expansion/differentiation. Two putative markers for islet precursor cells, UCHL1/PGP9.5 and DMBT1, were enhanced during the progression to differentiated cells, but only the latter could be a marker of islet precursor cells. We suggest that appropriate manipulation of these differentiation-associated pathways will enhance the efficiency of differentiation of insulin-producing beta-cells in this in vitro model.
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