scRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma

Nana Fatima Haruna, Yuliya Politanska, Andrew R. Connelly, Kathrine O'Connor, Sourav Bhattacharya, Grace E. Miklaszewski, Xóchitl G. Pérez-Leonor, Geddy Rerko, Ian T. Hentenaar, Doan C. Nguyen, Pedro Alberto Lamothe Molina, Bruce S. Bochner, Hiam Abdala-Valencia, Michelle A. Gill, F. Eun Hyung Lee, Sergejs Berdnikovs

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in trilobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that interleukin-5 promotes differentiation of immature blood neutrophils into trilobed eosinophilic phenotypes, suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.

Original languageEnglish
Pages (from-to)1184-1197
Number of pages14
JournalJournal of Leukocyte Biology
Volume116
Issue number5
DOIs
StatePublished - Nov 4 2024

Keywords

  • allergy
  • asthma
  • blood
  • bone marrow
  • emergency hematopoiesis
  • eosinophils
  • neutrophils
  • scRNA-seq

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