title: Transcriptomes of the major human pancreatic cell types.
abstract: OBJECTIVE
  We sought to determine the mRNA transcriptome of all major human pancreatic endocrine and exocrine cell subtypes, including human alpha, beta, duct and acinar cells. In addition, we identified the cell type-specific distribution of transcription factors, signalling ligands and their receptors.
  
  
  METHODS
  Islet samples from healthy human donors were enzymatically dispersed to single cells and labelled with cell type-specific surface-reactive antibodies. Live endocrine and exocrine cell subpopulations were isolated by FACS and gene expression analyses were performed using microarray analysis and quantitative RT-PCR. Computational tools were used to evaluate receptor-ligand representation in these populations.
  
  
  RESULTS
  Analysis of the transcriptomes of alpha, beta, large duct, small duct and acinar cells revealed previously unrecognised gene expression patterns in these cell types, including transcriptional regulators HOPX and HDAC9 in the human beta cell population. The abundance of some regulatory proteins was different from that reported in mouse tissue. For example, v-maf musculoaponeurotic fibrosarcoma oncogene homologue B (avian) (MAFB) was detected at equal levels in adult human alpha and beta cells, but is absent from adult mouse beta cells. Analysis of ligand-receptor interactions suggested that EPH receptor-ephrin communication between exocrine and endocrine cells contributes to pancreatic function.
  
  
  CONCLUSIONS
  This is the first comprehensive analysis of the transcriptomes of human exocrine and endocrine pancreatic cell types-including beta cells-and provides a useful resource for diabetes research. In addition, paracrine signalling pathways within the pancreas are shown. These results will help guide efforts to specify human beta cell fate by embryonic stem cell or induced pluripotent stem cell differentiation or genetic reprogramming.
authors: Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, L321, Portland, OR 97239, USA.
authors: C
authors: C
authors: Dorrell
authors: J
authors: J
authors: Schug
authors: C F
authors: CF
authors: Lin
authors: P S
authors: PS
authors: Canaday
authors: A J
authors: AJ
authors: Fox
authors: O
authors: O
authors: Smirnova
authors: R
authors: R
authors: Bonnah
authors: P R
authors: PR
authors: Streeter
authors: C J
authors: CJ
authors: Stoeckert
authors: K H
authors: KH
authors: Kaestner
authors: M
authors: M
authors: Grompe
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D046790:Pancreas, Exocrine / Q000166:cytology / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C476884:HOPX protein, human; D018398:Homeodomain Proteins; D008024:Ligands; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases