Redefinition of the human mast cell transcriptome by deep-CAGE sequencing

Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap analysis of gene expression on skin-derived MCs to generate the most comprehensive view of the human MC transcriptome ever reported. An advantage...

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Published in:Blood Vol. 123; no. 17; p. e58
Main Authors: Motakis, Efthymios, Guhl, Sven, Ishizu, Yuri, Itoh, Masayoshi, Kawaji, Hideya, de Hoon, Michiel, Lassmann, Timo, Carninci, Piero, Hayashizaki, Yoshihide, Zuberbier, Torsten, Forrest, Alistair R R, Babina, Magda
Format: Journal Article
Language:English
Published: United States 24.04.2014
Subjects:
Amino Acid Motifs
Bone Morphogenetic Proteins - metabolism
Cell Differentiation
Cell Lineage
Cluster Analysis
Databases, Factual
Genetic Markers
Hematopoiesis - genetics
Hematopoietic Stem Cells - cytology
High-Throughput Nucleotide Sequencing - methods
Humans
Immune System
Mast Cells - cytology
Multigene Family
Promoter Regions, Genetic
Sequence Analysis, DNA - methods
Skin - metabolism
Transcriptome
ISSN:1528-0020, 1528-0020
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Abstract Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap analysis of gene expression on skin-derived MCs to generate the most comprehensive view of the human MC transcriptome ever reported. An advantage is that MCs were embedded in the FANTOM5 project, giving the opportunity to contrast their molecular signature against a multitude of human samples. We demonstrate that MCs possess a unique and surprising transcriptional landscape, combining hematopoietic genes with those exclusively active in MCs and genes not previously reported as expressed by MCs (several of them markers of unrelated tissues). We also found functional bone morphogenetic protein receptors transducing activatory signals in MCs. Conversely, several immune-related genes frequently studied in MCs were not expressed or were weakly expressed. Comparing MCs ex vivo with cultured counterparts revealed profound changes in the MC transcriptome in in vitro surroundings. We also determined the promoter usage of MC-expressed genes and identified associated motifs active in the lineage. Befitting their uniqueness, MCs had no close relative in the hematopoietic network (also only distantly related with basophils). This rich data set reveals that our knowledge of human MCs is still limited, but with this resource, novel functional programs of MCs may soon be discovered.
AbstractList Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap analysis of gene expression on skin-derived MCs to generate the most comprehensive view of the human MC transcriptome ever reported. An advantage is that MCs were embedded in the FANTOM5 project, giving the opportunity to contrast their molecular signature against a multitude of human samples. We demonstrate that MCs possess a unique and surprising transcriptional landscape, combining hematopoietic genes with those exclusively active in MCs and genes not previously reported as expressed by MCs (several of them markers of unrelated tissues). We also found functional bone morphogenetic protein receptors transducing activatory signals in MCs. Conversely, several immune-related genes frequently studied in MCs were not expressed or were weakly expressed. Comparing MCs ex vivo with cultured counterparts revealed profound changes in the MC transcriptome in in vitro surroundings. We also determined the promoter usage of MC-expressed genes and identified associated motifs active in the lineage. Befitting their uniqueness, MCs had no close relative in the hematopoietic network (also only distantly related with basophils). This rich data set reveals that our knowledge of human MCs is still limited, but with this resource, novel functional programs of MCs may soon be discovered.Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap analysis of gene expression on skin-derived MCs to generate the most comprehensive view of the human MC transcriptome ever reported. An advantage is that MCs were embedded in the FANTOM5 project, giving the opportunity to contrast their molecular signature against a multitude of human samples. We demonstrate that MCs possess a unique and surprising transcriptional landscape, combining hematopoietic genes with those exclusively active in MCs and genes not previously reported as expressed by MCs (several of them markers of unrelated tissues). We also found functional bone morphogenetic protein receptors transducing activatory signals in MCs. Conversely, several immune-related genes frequently studied in MCs were not expressed or were weakly expressed. Comparing MCs ex vivo with cultured counterparts revealed profound changes in the MC transcriptome in in vitro surroundings. We also determined the promoter usage of MC-expressed genes and identified associated motifs active in the lineage. Befitting their uniqueness, MCs had no close relative in the hematopoietic network (also only distantly related with basophils). This rich data set reveals that our knowledge of human MCs is still limited, but with this resource, novel functional programs of MCs may soon be discovered.
Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap analysis of gene expression on skin-derived MCs to generate the most comprehensive view of the human MC transcriptome ever reported. An advantage is that MCs were embedded in the FANTOM5 project, giving the opportunity to contrast their molecular signature against a multitude of human samples. We demonstrate that MCs possess a unique and surprising transcriptional landscape, combining hematopoietic genes with those exclusively active in MCs and genes not previously reported as expressed by MCs (several of them markers of unrelated tissues). We also found functional bone morphogenetic protein receptors transducing activatory signals in MCs. Conversely, several immune-related genes frequently studied in MCs were not expressed or were weakly expressed. Comparing MCs ex vivo with cultured counterparts revealed profound changes in the MC transcriptome in in vitro surroundings. We also determined the promoter usage of MC-expressed genes and identified associated motifs active in the lineage. Befitting their uniqueness, MCs had no close relative in the hematopoietic network (also only distantly related with basophils). This rich data set reveals that our knowledge of human MCs is still limited, but with this resource, novel functional programs of MCs may soon be discovered.
Author de Hoon, Michiel
Guhl, Sven
Zuberbier, Torsten
Forrest, Alistair R R
Babina, Magda
Carninci, Piero
Kawaji, Hideya
Motakis, Efthymios
Ishizu, Yuri
Itoh, Masayoshi
Hayashizaki, Yoshihide
Lassmann, Timo
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  surname: Motakis
  fullname: Motakis, Efthymios
  organization: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan
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  fullname: Guhl, Sven
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  surname: Forrest
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– sequence: 12
  givenname: Magda
  surname: Babina
  fullname: Babina, Magda
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24671954$$D View this record in MEDLINE/PubMed
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Snippet Mast cells (MCs) mature exclusively in peripheral tissues, hampering research into their developmental and functional programs. Here, we employed deep cap...
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SubjectTerms Amino Acid Motifs
Bone Morphogenetic Proteins - metabolism
Cell Differentiation
Cell Lineage
Cluster Analysis
Databases, Factual
Genetic Markers
Hematopoiesis - genetics
Hematopoietic Stem Cells - cytology
High-Throughput Nucleotide Sequencing - methods
Humans
Immune System
Mast Cells - cytology
Multigene Family
Promoter Regions, Genetic
Sequence Analysis, DNA - methods
Skin - metabolism
Transcriptome
Title Redefinition of the human mast cell transcriptome by deep-CAGE sequencing
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