More than neutrophils: Lin(+)Ly6G(+)IL‐5Rα(+) multipotent myeloid cells (MMCs) are dominant in normal murine bone marrow and retain capacity to differentiate into eosinophils and monocytes. Issue 1 (15th April 2021)

• Record Type: Journal Article
• Authors: Jeong, Brian M.; Walker, Matthew T.; Rodriguez, Raul; Coden, Mackenzie E.; Nagasaka, Reina; Doan, Ton C.; Politanska, Yuliya; Abdala‐Valencia, Hiam; Berdnikovs, Sergejs
• Is Part Of: Journal of leukocyte biology. Volume 111:Issue 1(2022)
• Page Start: 113
• Page End: 122
• Publication Date: 2021-04-15
• Subjects: bone marrow -- eosinophils -- flow cytometry -- hematopoiesis -- heterogeneity -- homeostasis -- macrophages -- monocytes -- neutrophils -- plasticity -- transcription factors; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.1AB0519-170RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Bone marrow is a hematopoietic site harboring multiple populations of myeloid cells in different stages of differentiation. Murine bone marrow eosinophils are traditionally identified by Siglec‐F(+) staining using flow cytometry, whereas neutrophils are characterized by Ly6G(+) expression. However, using flow cytometry to characterize bone marrow hematopoietic cells in wild‐type mice, we found substantial gray areas in identification of these cells. Siglec‐F(+) mature eosinophil population constituted only a minority of bone marrow Lin(+)CD45(+) pool (5%). A substantial population of Siglec‐F(−) cells was double positive for neutrophil marker Ly6G and eosinophil lineage marker, IL‐5Rα. This granulocyte population with mixed neutrophil and eosinophil characteristics is typically attributable to neutrophil pool based on neutral granule staining and expression of Ly6G and myeloid peroxidase. It is distinct from Lineage(−) myeloid progenitors or Siglec‐F(+)Ly6G(+) maturing eosinophil precursors, and can be accurately identified by Lineage(+) staining and positive expression of markers IL‐5Rα and Ly6G. At 15–50% of all CD45(+) hematopoietic cells in adult mice (percentage varies by sex and age), this is a surprisingly dominant population, which increases with age in both male and female mice. RNA‐seq characterization of these cells revealed a complex immune profile and the capacity to secrete constituents of the extracellular matrix. When sorted from bone marrow, these resident cells had neutrophilic phenotype but readily acquired all characteristics of eosinophils when cultured with G‐CSF or IL‐5, including expression of Siglec‐F and granular proteins (Epx, Mbp). Surprisingly, these cells were also able to differentiate into Ly6C(+) monocytes when cultured with M‐CSF. Herein described is the discovery of an unexpected hematopoietic flexibility of a dominant population of multipotent myeloid cells, typically categorized as neutrophils, but with the previously unknown plasticity to contribute to mature pools of eosinophils and monocytes. Graphical Abstract: Characterization of neutrophil‐like Lin(+)Ly6G(+)IL‐5Rα(+) population in normal murine bone marrow reveals its unexpected myeloid plasticity with substantial potential to differentiate to mature eosinophils and monocytes