Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis.
Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the beta7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil/mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells. We also identified the basophil progenitor (BaP) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays a primary role in the fate decision of BMCPs, being expressed in BaPs but not in MCPs. Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C/EBPalpha.
Arinobu
Yojiro
Y
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Iwasaki
Hiromi
H
Gurish
Michael F
MF
Mizuno
Shin-ichi
S
Shigematsu
Hirokazu
H
Ozawa
Hidetoshi
H
Tenen
Daniel G
DG
Austen
K Frank
KF
Akashi
Koichi
K
D000818:Animals; D001854:Bone Marrow Cells; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology; D014234:Trichinella / Q000276:immunology
D022763:CCAAT-Enhancer-Binding Protein-alpha; D039641:Integrin beta Chains; C091368:integrin beta7; D010047:Ovalbumin