title: Redefinition of the human mast cell transcriptome by deep-CAGE sequencing.
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.
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan;
authors.forename: Efthymios
authors.initials: E
authors.lastname: Motakis
authors.forename: Sven
authors.initials: S
authors.lastname: Guhl
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ishizu
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.forename: Michiel
authors.initials: M
authors.lastname: de Hoon
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Torsten
authors.initials: T
authors.lastname: Zuberbier
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Magda
authors.initials: M
authors.lastname: Babina
mesh_terms: D020816:Amino Acid Motifs; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D016000:Cluster Analysis; D016208:Databases, Factual; D005819:Genetic Markers; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007107:Immune System; D008407:Mast Cells / Q000166:cytology*; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D012867:Skin / Q000378:metabolism; D059467:Transcriptome
chemical_list: D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers