Synergizing genomic analysis with biological knowledge to identify and validate novel genes in pancreatic development

Pancreas. 2012 Aug;41(6):962-9. doi: 10.1097/MPA.0b013e31823d0160.

Abstract

Objective: This study investigated the utility of advanced computational techniques to large-scale genome-based data to identify novel genes that govern murine pancreatic development.

Methods: An expression data set for mouse pancreatic development was complemented with high-throughput data analyzer to identify and prioritize novel genes. Quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to validate selected genes.

Results: Four new genes whose roles in the development of murine pancreas have not previously been established were identified: cystathionine β-synthase (Cbs), Meis homeobox 1, growth factor independent 1, and aldehyde dehydrogenase 18 family, member A1. Their temporal expression during development was documented. Cbs was localized in the cytoplasm of the tip cells of the epithelial chords of the undifferentiated progenitor cells at E12.5 and was coexpressed with the pancreatic and duodenal homeobox 1 and pancreas-specific transcription factor, 1a-positive cells. In the adult pancreas, Cbs was localized primarily within the acinar compartment.

Conclusions: In silico analysis of high-throughput microarray data in combination with background knowledge about genes provides an additional reliable method of identifying novel genes. To our knowledge, the expression and localization of Cbs have not been previously documented during mouse pancreatic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Computational Biology
  • Cystathionine beta-Synthase / genetics
  • Cystathionine beta-Synthase / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Genomics* / methods
  • Gestational Age
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Morphogenesis / genetics*
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pancreas / embryology
  • Pancreas / growth & development
  • Pancreas / metabolism*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Gfi1 protein, mouse
  • Homeodomain Proteins
  • Myeloid Ecotropic Viral Integration Site 1 Protein
  • Neoplasm Proteins
  • RNA, Messenger
  • Transcription Factors
  • Aldehyde Dehydrogenase
  • Cystathionine beta-Synthase