PUBLICATION

Transcriptome analysis of pancreatic cells across distant species highlights novel important regulator genes

Authors
Tarifeño-Saldivia, E., Lavergne, A., Bernard, A., Padamata, K., Bergemann, D., Voz, M.L., Manfroid, I., Peers, B.
ID
ZDB-PUB-170323-8
Date
2017
Source
BMC Biology   15: 21 (Journal)
Registered Authors
Bergemann, David, Bernard, Alice, Lavergne, Arnaud, Manfroid, Isabelle, Peers, Bernard, Voz, Marianne
Keywords
Acinar cells, Comparative transcriptomics, Ductal cells, Endocrine cells, Pancreas, RNA-seq
MeSH Terms
  • Pancreas/cytology*
  • Pancreas/metabolism*
  • Genetic Markers
  • Acinar Cells/cytology
  • Acinar Cells/metabolism
  • Mutation/genetics
  • Glucagon-Secreting Cells/cytology
  • Glucagon-Secreting Cells/metabolism
  • Transcription Factors/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Animals
  • Gene Expression Profiling/methods*
  • Principal Component Analysis
  • Insulin-Secreting Cells/cytology
  • Insulin-Secreting Cells/metabolism
  • Cell Differentiation/genetics
  • Cell Separation
  • Glucagon/metabolism
  • Humans
  • Mice
  • Embryo, Nonmammalian/metabolism
  • Species Specificity
  • Genes, Regulator*
  • Gene Expression Regulation, Developmental
  • Evolution, Molecular
(all 26)
PubMed
28327131 Full text @ BMC Biol.
Abstract
Defining the transcriptome and the genetic pathways of pancreatic cells is of great interest for elucidating the molecular attributes of pancreas disorders such as diabetes and cancer. As the function of the different pancreatic cell types has been maintained during vertebrate evolution, the comparison of their transcriptomes across distant vertebrate species is a means to pinpoint genes under strong evolutionary constraints due to their crucial function, which have therefore preserved their selective expression in these pancreatic cell types.
In this study, RNA-sequencing was performed on pancreatic alpha, beta, and delta endocrine cells as well as the acinar and ductal exocrine cells isolated from adult zebrafish transgenic lines. Comparison of these transcriptomes identified many novel markers, including transcription factors and signaling pathway components, specific for each cell type. By performing interspecies comparisons, we identified hundreds of genes with conserved enriched expression in endocrine and exocrine cells among human, mouse, and zebrafish. This list includes many genes known as crucial for pancreatic cell formation or function, but also pinpoints many factors whose pancreatic function is still unknown. A large set of endocrine-enriched genes can already be detected at early developmental stages as revealed by the transcriptomic profiling of embryonic endocrine cells, indicating a potential role in cell differentiation. The actual involvement of conserved endocrine genes in pancreatic cell differentiation was demonstrated in zebrafish for myt1b, whose invalidation leads to a reduction of alpha cells, and for cdx4, selectively expressed in endocrine delta cells and crucial for their specification. Intriguingly, comparison of the endocrine alpha and beta cell subtypes from human, mouse, and zebrafish reveals a much lower conservation of the transcriptomic signatures for these two endocrine cell subtypes compared to the signatures of pan-endocrine and exocrine cells. These data suggest that the identity of the alpha and beta cells relies on a few key factors, corroborating numerous examples of inter-conversion between these two endocrine cell subtypes.
This study highlights both evolutionary conserved and species-specific features that will help to unveil universal and fundamental regulatory pathways as well as pathways specific to human and laboratory animal models such as mouse and zebrafish.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz18TgTransgenic Insertion
    ia1TgTransgenic Insertion
      jh1TgTransgenic Insertion
        jh4TgTransgenic Insertion
          tv205c
            Small Deletion
            ulg004TgTransgenic Insertion
              ulg021TgTransgenic Insertion
                ulg029
                  Insertion
                  ulg515TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    myt1aCRISPR1-myt1aCRISPR
                    myt1aCRISPR2-myt1aCRISPR
                    myt1bCRISPR1-myt1bCRISPR
                    myt1bCRISPR2-myt1bCRISPR
                    1 - 4 of 4
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                    Fish
                    Antibodies
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    mCherryEFGmCherry
                    NTREFGNTR
                    1 - 4 of 4
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                    Mapping
                    No data available