Single cell transcriptomics clarifies the basophil differentiation trajectory and identifies pre-basophils upstream of mature basophils

Kensuke Miyake (), Junya Ito, Jun Nakabayashi, Shigeyuki Shichino, Kenji Ishiwata and Hajime Karasuyama
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Kensuke Miyake: Tokyo Medical and Dental University (TMDU)
Junya Ito: Tokyo Medical and Dental University (TMDU)
Jun Nakabayashi: Tokyo Medical and Dental University (TMDU)
Shigeyuki Shichino: Tokyo University of Science
Kenji Ishiwata: The Jikei University School of Medicine
Hajime Karasuyama: Tokyo Medical and Dental University (TMDU)

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Basophils are the rarest granulocytes and are recognized as critical cells for type 2 immune responses. However, their differentiation pathway remains to be fully elucidated. Here, we assess the ontogenetic trajectory of basophils by single-cell RNA sequence analysis. Combined with flow cytometric and functional analyses, we identify c-Kit-CLEC12Ahi pre-basophils located downstream of pre-basophil and mast cell progenitors (pre-BMPs) and upstream of CLEC12Alo mature basophils. The transcriptomic analysis predicts that the pre-basophil population includes previously-defined basophil progenitor (BaP)-like cells in terms of gene expression profile. Pre-basophils are highly proliferative and respond better to non-IgE stimuli but less to antigen plus IgE stimulation than do mature basophils. Although pre-basophils usually remain in the bone marrow, they emerge in helminth-infected tissues, probably through IL-3-mediated inhibition of their retention in the bone marrow. Thus, the present study identifies pre-basophils that bridge the gap between pre-BMPs and mature basophils during basophil ontogeny.

Date: 2023
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DOI: 10.1038/s41467-023-38356-1

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