Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors

Immunity. 2018 Oct 16;49(4):640-653.e5. doi: 10.1016/j.immuni.2018.09.023.


Tissue-resident mast cells are associated with many inflammatory and physiological processes. Although mast cells arise from the yolk sac, the exact ontogeny of adult mast cells remains unclear. Here we have investigated the hematopoietic origin of mast cells using fate-mapping systems. We have shown that early erythro-myeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells (HSCs) each gave rise to mast cells in succession via an intermediate integrin β7+ progenitor. From late embryogenesis to adult, early EMP-derived mast cells were largely replaced by late EMP-derived cells in most connective tissues except adipose and pleural cavity. Thus, mast cells with distinct origin displayed tissue-location preferences: early EMP-derived cells were limited to adipose and pleural cavity and late EMP-derived cells dominated most connective tissues, while HSC-derived cells were a main group in mucosa. Therefore, embryonic origin shapes the heterogeneity of adult mast cells, with diverse functions in immunity and development.

Keywords: Erythro-myeloid progenitors; Hematopoietic stem cells; Mast cell-committed progenitors; Mast cells; Ontogeny; Yolk sac.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage / immunology
  • Cells, Cultured
  • Connective Tissue / immunology
  • Connective Tissue / metabolism
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / immunology
  • Erythroid Cells / cytology
  • Erythroid Cells / immunology*
  • Erythroid Cells / metabolism
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Integrin beta Chains / immunology
  • Integrin beta Chains / metabolism
  • Mast Cells / cytology
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mice, Transgenic
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / immunology*
  • Myeloid Progenitor Cells / metabolism


  • Integrin beta Chains
  • integrin beta7