Identification of a Siglec-F+ granulocyte-macrophage progenitor

J Leukoc Biol. 2018 Jul;104(1):123-133. doi: 10.1002/JLB.1MA1217-475R. Epub 2018 Apr 12.

Abstract

In recent years multi-parameter flow cytometry has enabled identification of cells at major stages in myeloid development; from pluripotent hematopoietic stem cells, through populations with increasingly limited developmental potential (common myeloid progenitors and granulocyte-macrophage progenitors), to terminally differentiated mature cells. Myeloid progenitors are heterogeneous, and the surface markers that define transition states from progenitors to mature cells are poorly characterized. Siglec-F is a surface glycoprotein frequently used in combination with IL-5 receptor alpha (IL5Rα) for the identification of murine eosinophils. Here, we describe a CD11b+ Siglec-F+ IL5Rα- myeloid population in the bone marrow of C57BL/6 mice. The CD11b+ Siglec-F+ IL5Rα- cells are retained in eosinophil deficient PHIL mice, and are not expanded upon overexpression of IL-5, indicating that they are upstream or independent of the eosinophil lineage. We show these cells to have GMP-like developmental potential in vitro and in vivo, and to be transcriptionally distinct from the classically described GMP population. The CD11b+ Siglec-F+ IL5Rα- population expands in the bone marrow of Myb mutant mice, which is potentially due to negative transcriptional regulation of Siglec-F by Myb. Lastly, we show that the role of Siglec-F may be, at least in part, to regulate GMP viability.

Keywords: Myb; eosinophil; granulocyte; hematopoiesis; neutrophil.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Granulocyte-Macrophage Progenitor Cells / cytology*
  • Granulocyte-Macrophage Progenitor Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Sialic Acid Binding Immunoglobulin-like Lectins / metabolism*

Substances

  • Sialic Acid Binding Immunoglobulin-like Lectins