Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis

Yojiro Arinobu, Hiromi Iwasaki, Michael F. Gurish, Shin Ichi Mizuno, Hirokazu Shigematsu, Hidetoshi Ozawa, Daniel G. Tenen, K. Frank Austen, Koichi Akashi

Research output: Contribution to journalArticle

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Abstract

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 β7 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 α (C/EBPα) 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/EBPα.

Original languageEnglish
Pages (from-to)18105-18110
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number50
DOIs
Publication statusPublished - Dec 13 2005

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Basophils
Hematopoiesis
Cell Lineage
Mast Cells
CCAAT-Enhancer-Binding Proteins
Mucous Membrane
Connective Tissue Cells
IgE Receptors
Adaptive Immunity
Granulocytes
Innate Immunity
Integrins
Transcription Factors
Stem Cells
Spleen
Bone Marrow

All Science Journal Classification (ASJC) codes

  • General

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Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. / Arinobu, Yojiro; Iwasaki, Hiromi; Gurish, Michael F.; Mizuno, Shin Ichi; Shigematsu, Hirokazu; Ozawa, Hidetoshi; Tenen, Daniel G.; Austen, K. Frank; Akashi, Koichi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 50, 13.12.2005, p. 18105-18110.

Research output: Contribution to journalArticle

Arinobu, Yojiro ; Iwasaki, Hiromi ; Gurish, Michael F. ; Mizuno, Shin Ichi ; Shigematsu, Hirokazu ; Ozawa, Hidetoshi ; Tenen, Daniel G. ; Austen, K. Frank ; Akashi, Koichi. / Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 50. pp. 18105-18110.
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