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

Area of Science:

• Immunology
• Cell Biology
• Hematology

Background:

• Mast cells (MC) are crucial immune cells involved in health and disease.
• In vitro studies often use bone marrow-derived MC (BMMC), but these differ from in vivo tissue-resident MC.
• Understanding MC heterogeneity is vital for accurate disease modeling.

Purpose of the Study:

• To compare BMMC, fetal skin MC (FSMC), and fetal liver MC (FLMC) as in vitro models for mature connective tissue MC (CTMC).
• To identify the best surrogate for studying CTMC in vitro.
• To investigate the impact of tissue origin on MC development and function.

Main Methods:

• Side-by-side culture of BMMC, FSMC, and FLMC.
• Histological analysis for morphology.
• Flow cytometry for MC phenotype.
• Transcriptome analysis.
• Assessment of ST2 expression and cytokine secretion.
• Measurement of granule content, FcεRI activation response, and histamine release.

Main Results:

• All MC types exhibited comparable morphology and phenotype.
• Transcriptomic analysis revealed significant differences, notably in Hdc and Tpsb2 expression in FSMC.
• FSMC and BMMC showed high ST2 expression, unlike FLMC, impacting type 2 cytokine secretion.
• FSMC demonstrated higher granule content, FcεRI activation response, and histamine release compared to FLMC and BMMC.

Conclusions:

• Tissue of origin significantly imprints mast cell precursor cells, leading to distinct phenotypes and signatures even under identical culture conditions.
• Fetal-derived MC, particularly FSMC, more closely resemble mature CTMC than BMMC.
• FSMC represent the most developed in vitro model for studying mature connective tissue MC.