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

Abstract

Graphical AbstractHighlights d Three waves of fetal hematopoiesis contribute to fetal mast cells in succession d The three origin-derived mast cells have distinct tissue preferences d Integrin b7 + CD117 + CD11b low cells are embryonic mast cell precursors d Late EMP-derived mast cells are the major composition of adult CTMCs SUMMARY 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 b7 + 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 EMPderived 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.

Emerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation

“…The part of the hematopoietic development and differentiation system that leads to major myeloid cell types within the immune system including granulocytes, monocytes, and dendritic cells is termed myelopoiesis Ginhoux and Jung, 2014;Paul et al, 2015;Schlitzer and Ginhoux, 2014;Schultze and Beyer, 2016). Essentially all myeloid cells-particularly in the adult individual-are derived via myelopoiesis from HSCs, with two exceptions: yolk-sac-derived tissue macrophages (Geissmann and Mass, 2015;Ginhoux et al, 2010;Ginhoux and Jung, 2014;Guilliams et al, 2014;Schlitzer et al, 2015a) and resident mast cells (Gentek et al, 2018;Li et al, 2018). During homeostasis, hundreds of millions of neutrophils and monocytes are generated via myelopoiesis; however, there is still only limited understanding of the many factors involved in regulating this enormous cellular output (Furze and Rankin, 2008;Manz and Boettcher, 2014).…”

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…This is a wonderful time in mast cell research. Indeed, the last years have witnessed unprecedented progress in our understanding of the development of mast cells [40][41][42]. Moreover, extraordinary progress has been made in understanding the complex homeostatic and protective roles of these cells in different pathophysiological conditions [31,39,114,115].…”

“…We would like to speculate that such different, sometime opposite effects of mast cells are made possible by the plurality of mast cell subpopulations. Recently, comprehensive analysis of the transcriptome of individual anatomically distinct mast cells [117] and fate-mapping system [40,41,118] demonstrate that rodent mast cells form a highly heterogeneous population of immune cells [40][41][42], similar to macrophages [43,119] and T cells [120,121]. These fascinating results indicate that much more remains to be discovered in development, migration to tissues, biochemistry, and functions of different subsets of rodent and human mast cells.…”

“…This volume contains contributions by several established investigators in the field of mast cell biology. The volume starts with a collaborative paper by Stephen J. Galli, Gilda Varricchi, and Gianni Marone, illustrating initial and more recent studies which have attempted to identify distinct "subpopulations" of mast cells based on the analyses of transcriptomes of anatomically distinct mouse mast cell populations [39][40][41][42]. The authors illustrate the important roles played by mast cells to the control of homeostasis in different pathophysiological conditions.…”

Localization-Specific Expression of CCR1 and CCR5 by Mast Cell Progenitors

“…In embryonic development, the first mast cells that populate the tissues derive from progenitors in the yolk sac (1). In adult mice, mast cells seem to have a dual origin with long-lived connective tissue type mast cells mainly originating from yolk sac-derived mast cell progenitors (MCp), and mucosal mast cells developing from bone marrow-derived MCp that originate from fetal hematopoietic stem cells (2). In humans, a MCp population is present in peripheral blood and bone marrow (3,4).…”