Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism [RNA-seq]

ABSTRACT: Here we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.

ORGANISM(S): Homo sapiens

SUBMITTER: Joao Fadista

PROVIDER: E-GEOD-50244 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TCF7L2 is a master regulator of insulin production and processing.

Zhou Yuedan Y Park Soo-Young SY Su Jing J Bailey Kathleen K Ottosson-Laakso Emilia E Shcherbina Liliya L Oskolkov Nikolay N Zhang Enming E Thevenin Thomas T Fadista João J Fadista João J Bennet Hedvig H Vikman Petter P Wierup Nils N Fex Malin M Rung Johan J Wollheim Claes C Nobrega Marcelo M Renström Erik E Groop Leif L Hansson Ola O

Human molecular genetics 20140711 24

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and ...[more]

PMID: 25015099

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Project description:Previous studies have suggested that Bmp4 is a key Msx1-dependent mesenchymal odontogenic signal for driving tooth morphogenesis through the bud-to-cap transition. Whereas the bud stage tooth developmental arrest in Msx1-/- mutant mice was accompanied by reduction in mesenchymal Bmp4 mRNA expression, we show that depleting functional Bmp4 mRNAs in the tooth mesenchyme, through neural crest-specific gene inactivation in Bmp4f/f;Wnt1Cre mice, caused mandibular molar developmental arrest at the bud stage but allowed maxillary molars and incisors to develop to mineralized teeth. We show that the Wnt inhibitors Dkk2 and Wif1 were much more abundantly expressed in the mandibular than maxillary molar mesenchyme in wildtype embryos and that Dkk2 expression was significantly unregulated in the tooth mesenchyme in Bmp4f/f;Wnt1Cre embryos. In addition, expression of Osr2, which encodes a zinc finger protein that antagonizes Msx1-mediated activation of odontogenic mesenchyme, is significantly upregulated in the molar mesenchyme in Bmp4f/f;Wnt1Cre embryos. Msx1 heterozygosity enhanced maxillary molar developmental defects whereas Osr2 heterozygosity rescued mandibular first molar morphogenesis in Bmp4f/f;Wnt1Cre mice. Moreover, in contrast to complete lack of supernumerary tooth initiation in Msx1-/-Osr2-/- mutant mice, Osr2-/-Bmp4f/f;Wnt1Cre compound mutant mice exhibit formation and subsequent arrest of supernumerary tooth germs that correlated with down regulation of Msx1 expression in the tooth mesenchyme. Taken together, our data indicate that, while reduction in mesenchymal Bmp4 expression alone could not account for the tooth bud arrest phenotype in Msx1-/- mutant mice, Bmp4 signaling synergizes with Msx1 and antagonizes Osr2 to activate mesenchymal odontogenic activity to drive tooth morphogenesis and sequential tooth formation. E13.5 mouse embryos tooth germs were microdissected by laser capture microdissection (LCM), and the mandibular molar and maxillary molar were separated. 3 pairs of control and mutant samples were pooled for the RNA extraction.

Dataset Information

Global transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism [RNA-seq]

Publications

TCF7L2 is a master regulator of insulin production and processing.

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