Skin mast cells develop non‐synchronized changes in typical lineage characteristics upon culture

Despite their hematopoietic origin, mast cells (MCs) develop exclusively in tissues, hampering their ample use in research. To circumvent this problem, tissue‐derived MCs are typically first expanded in culture, but the changes MCs may undergo in the novel micromilieu are poorly defined. Here, we monitor skin MCs from a number of donors over time, revealing profound yet non‐synchronized modulations in culture. While tryptase and chymase, the most specific markers, strongly decline, FcεRI surface expression, and FcεRI‐mediated histamine release steeply increase (from ≈15.5% to ≈60%), replicated by similar increments in TNF‐α secretion. Interestingly, the modulations are independent of cell cycle progression, as they are comparable in the growth and postgrowth phase, implying they primarily result from microenvironmental conditioning. The data highlight a high degree of MC versatility, but also advise that results based on cultured MCs should be viewed with some caution, as they may not accurately reflect their counterparts in situ.