Researchers have proposed a possible explanation for the variation in FcεRI expression during the development of mast cells, suggesting that external stimuli regulate the FcεRI expression of mast cell progenitors,
Many diseases, such as asthma and systemic mastocytosis, are driven by mast cells. The current understanding is that mast cell progenitors exhibit low FcεRI expression, if any at all. The unresolved question is the point in the progenitor stage at which FcεRI expression occurs. Conflicting studies differ on whether FcεRI is an early or late event during the differentiation of mast cells.
The authors of the present study, published in Blood Advances, hence decided to chart human hematopoiesis, with special attention afforded to the differentiation of mast cell progenitors. In addition, they wanted to study the expression of FcεRI during mast cell development and understand the factors that regulate mast cell progenitors.
The research team extracted cells from healthy donors. They used single-cell transcriptomics analysis to identify any association between the expression of FcεRI and the mast cell gene signature. The analysis was performed on CD34+ hematopoietic progenitors in adult peripheral blood.
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Wu et al discovered that the expression of FcεRI occurred at the progenitor stage of mast cell differentiation in adult peripheral blood. They also found that FcεRI expression is regulated by external stimuli, which explains why different scientists have reported FcεRI expression at various stages of mast cell development.
“The single-cell transcriptomics datasets presented with this investigation provide the research community with a high-resolution map of hematopoietic progenitor differentiation with focus on the rare mast cell progenitor population,” Wu and colleagues wrote. “These data provide definitive proof that FcεRI may appear already at the mast cell progenitor stage, before terminal mast cell maturation.”
Wu C, Boey D, Bril O, et al. Single-cell transcriptomics reveals the identity and regulators of human mast cell progenitors. Blood Adv. 2022;bloodadvances.2022006969. doi:10.1182/bloodadvances.2022006969