Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Efthymios Motakis1,
  2. Sven Guhl2,
  3. Yuri Ishizu3,
  4. Masayoshi Itoh1,
  5. Hideya Kawaji4,
  6. Michiel de Hoon1,
  7. Timo Lassmann1,
  8. Piero Carninci1,
  9. Yoshihide Hayashizaki1,
  10. Torsten Zuberbier2,
  11. Alistair R. R. Forrest1,*, and
  12. Magda Babina2
  1. 1 RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan;
  2. 2 Department of Dermatology and Allergy, Charite Universitaetsmedizin Berlin, Berlin, Germany;
  3. 3 RIKEN Omics Science Center, Yokohama, Kanagawa, Japan;
  4. 4 RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan
  1. * Corresponding author; email: alistair.forrest{at}gmail.com

Key points

  • Generated a reference transcriptome for ex vivo, cultured, and stimulated mast cells, contrasted against a broad collection of primary cells.

  • Identified BMPs as function-modulating factors for mast cells.

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.

  • Submitted February 8, 2013.
  • Accepted June 19, 2013.