Fetal Tissue-Derived Mast Cells (MC) as Experimental Surrogate for In Vivo Connective Tissue MC

Caterina Iuliano, Magdalena Absmaier-Kijak, Tobias Sinnberg, Nils Hoffard, Miriam Hils, Martin Köberle, Florian Wölbing, Ekaterina Shumilina, Nicole Heise, Birgit Fehrenbacher, Martin Schaller, Florian Lang, Susanne Kaesler, Tilo Biedermann

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Bone-marrow-derived mast cells are matured from bone marrow cells in medium containing 20% fetal calf serum (FCS), interleukin (IL)-3 and stem-cell factor (SCF) and are used as in vitro models to study mast cells (MC) and their role in health and disease. In vivo, however, BM-derived hematopoietic stem cells account for only a fraction of MC; the majority of MC in vivo are and remain tissue resident. In this study we established a side-by-side culture with BMMC, fetal skin MC (FSMC) or fetal liver MC (FLMC) for comparative studies to identify the best surrogates for mature connective tissue MC (CTMC). All three MC types showed comparable morphology by histology and MC phenotype by flow cytometry. Heterogeneity was detected in the transcriptome with the most differentially expressed genes in FSMC compared to BMMC being Hdc and Tpsb2. Expression of ST2 was highly expressed in BMMC and FSMC and reduced in FLMC, diminishing their secretion of type 2 cytokines. Higher granule content, stronger response to FcεRI activation and significantly higher release of histamine from FSMC compared to FLMC and BMMC indicated differences in MC development in vitro dependent on the tissue of origin. Thus, tissues of origin imprint MC precursor cells to acquire distinct phenotypes and signatures despite identical culture conditions. Fetal-derived MC resemble mature CTMC, with FSMC being the most developed.

Original languageEnglish
Article number928
JournalCells
Volume11
Issue number6
DOIs
StatePublished - 2 Mar 2022
Externally publishedYes

Keywords

  • IgE
  • In vitro model
  • Mast cell
  • Proteases
  • RNA sequencing
  • Transcriptome

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