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Single‐cell molecular profiling provides a high‐resolution map of basophil and mast cell development

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Hamey, Fiona K. 
Lau, Winnie W.Y. 
Kucinski, Iwo 
Wang, Xiaonan 
Diamanti, Evangelia 


Abstract: Background: Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector cells are extensively studied, the differentiation trajectories from hematopoietic progenitors to basophils and mast cells are largely uncharted at the single‐cell level. Methods: We performed multicolor flow cytometry, high‐coverage single‐cell RNA sequencing analyses, and cell fate assays to chart basophil and mast cell differentiation at single‐cell resolution in mouse. Results: Analysis of flow cytometry data reconstructed a detailed map of basophil and mast cell differentiation, including a bifurcation of progenitors into two specific trajectories. Molecular profiling and pseudotime ordering of the single cells revealed gene expression changes during differentiation. Cell fate assays showed that multicolor flow cytometry and transcriptional profiling successfully predict the bipotent phenotype of a previously uncharacterized population of peritoneal basophil‐mast cell progenitors. Conclusions: A combination of molecular and functional profiling of bone marrow and peritoneal cells provided a detailed road map of basophil and mast cell development. An interactive web resource was created to enable the wider research community to explore the expression dynamics for any gene of interest.


Funder: Karolinska Institutet

Funder: Magnus Bergvall Foundation

Funder: Lars Hierta Memorial Foundation

Funder: Swedish Cancer Society

Funder: Åke Wiberg Foundation


ORIGINAL ARTICLE, ORIGINAL ARTICLES, basophils, differentiation, mast cells, single‐cell RNA sequencing, transcriptomics

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Wellcome (206328/Z/17/Z)
Core funding from Wellcome (100140/Z/12/Z)
MRC (MR/S036113/1)
Swedish Research Council (2015‐06322, 2018‐02070)
MRC Physical Biology of Stem Cells (MR/K500975/1)
Wellcome Strategic Award (105031/D/14/Z)
CRUK (C1163/A21762)
Core funding from Wellcome and MRC (203151/Z/16/Z)
NIH‐NIDDK (1 R24 DK106766)
Blood Cancer UK (18002)