4.7 Article

Landscape of mast cell populations across organs in mice and humans

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 220, Issue 10, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20230570

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By combining whole-tissue imaging and single-cell RNA sequencing datasets, this study provides a comprehensive analysis of mast cells in mice and humans. The results reveal the presence of two distinct mast cell populations in mice and seven different mast cell subsets in humans, with specific transcriptomic signatures. This study sheds light on the natural diversity of mast cell subtypes and provides valuable insights for studying mast cell functions and diseases.
Mast cells (MCs) are tissue-resident immune cells that exhibit homeostatic and neuron-associated functions. Here, we combined whole-tissue imaging and single-cell RNA sequencing datasets to generate a pan-organ analysis of MCs in mice and humans at steady state. In mice, we identify two mutually exclusive MC populations, MrgprB2(+) connective tissue-type MCs and MrgprB2(neg) mucosal-type MCs, with specific transcriptomic core signatures. While MrgprB2(+) MCs develop in utero independently of the bone marrow, MrgprB2(neg) MCs develop after birth and are renewed by bone marrow progenitors. In humans, we unbiasedly identify seven MC subsets (MC1-7) distributed across 12 organs with different transcriptomic core signatures. MC1 are preferentially enriched in the bladder, MC2 in the lungs, and MC4, MC6, and MC7 in the skin. Conversely, MC3 and MC5 are shared by most organs but not skin. This comprehensive analysis offers valuable insights into the natural diversity of MC subtypes in both mice and humans. Combining whole-tissue imaging and single-cell RNA sequencing datasets, Tauber et al. present a pan-organ analysis of mast cells in mice and humans at steady state, revealing an unexpected heterogeneity of mast cell populations across tissues and species.

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