Identification of a Siglec-F+ granulocyte-macrophage progenitor

Jessica E. Bolden, Erin C. Lucas, Geyu Zhou, Jeremy Alastair O'Sullivan, Carolyn A. de Graaf, Mark D. McKenzie, Ladina Di Rago, Tracey M. Baldwin, Jake Shortt, Warren S. Alexander, Bruce Scott Bochner, Matthew E. Ritchie, Douglas J. Hilton, Kirsten A. Fairfax

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)123-133
Number of pages11
JournalJournal of Leukocyte Biology
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2018

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Sialic Acid Binding Immunoglobulin-like Lectins
Granulocyte-Macrophage Progenitor Cells
Interleukin-5 Receptors
Eosinophils
Population
Bone Marrow
Myeloid Progenitor Cells
Pluripotent Stem Cells
Interleukin-5
Membrane Glycoproteins
Hematopoietic Stem Cells
Inbred C57BL Mouse
Flow Cytometry

Keywords

  • Myb
  • eosinophil
  • granulocyte
  • hematopoiesis
  • neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Bolden, J. E., Lucas, E. C., Zhou, G., O'Sullivan, J. A., de Graaf, C. A., McKenzie, M. D., ... Fairfax, K. A. (2018). Identification of a Siglec-F+ granulocyte-macrophage progenitor. Journal of Leukocyte Biology, 104(1), 123-133. https://doi.org/10.1002/JLB.1MA1217-475R
Bolden, Jessica E. ; Lucas, Erin C. ; Zhou, Geyu ; O'Sullivan, Jeremy Alastair ; de Graaf, Carolyn A. ; McKenzie, Mark D. ; Di Rago, Ladina ; Baldwin, Tracey M. ; Shortt, Jake ; Alexander, Warren S. ; Bochner, Bruce Scott ; Ritchie, Matthew E. ; Hilton, Douglas J. ; Fairfax, Kirsten A. / Identification of a Siglec-F+ granulocyte-macrophage progenitor. In: Journal of Leukocyte Biology. 2018 ; Vol. 104, No. 1. pp. 123-133.
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Bolden, JE, Lucas, EC, Zhou, G, O'Sullivan, JA, de Graaf, CA, McKenzie, MD, Di Rago, L, Baldwin, TM, Shortt, J, Alexander, WS, Bochner, BS, Ritchie, ME, Hilton, DJ & Fairfax, KA 2018, 'Identification of a Siglec-F+ granulocyte-macrophage progenitor' Journal of Leukocyte Biology, vol. 104, no. 1, pp. 123-133. https://doi.org/10.1002/JLB.1MA1217-475R

Identification of a Siglec-F+ granulocyte-macrophage progenitor. / Bolden, Jessica E.; Lucas, Erin C.; Zhou, Geyu; O'Sullivan, Jeremy Alastair; de Graaf, Carolyn A.; McKenzie, Mark D.; Di Rago, Ladina; Baldwin, Tracey M.; Shortt, Jake; Alexander, Warren S.; Bochner, Bruce Scott; Ritchie, Matthew E.; Hilton, Douglas J.; Fairfax, Kirsten A.

In: Journal of Leukocyte Biology, Vol. 104, No. 1, 01.07.2018, p. 123-133.

Research output: Contribution to journalArticle

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T1 - Identification of a Siglec-F+ granulocyte-macrophage progenitor

AU - Bolden, Jessica E.

AU - Lucas, Erin C.

AU - Zhou, Geyu

AU - O'Sullivan, Jeremy Alastair

AU - de Graaf, Carolyn A.

AU - McKenzie, Mark D.

AU - Di Rago, Ladina

AU - Baldwin, Tracey M.

AU - Shortt, Jake

AU - Alexander, Warren S.

AU - Bochner, Bruce Scott

AU - Ritchie, Matthew E.

AU - Hilton, Douglas J.

AU - Fairfax, Kirsten A.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

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