Identification of a Siglec-F+ granulocyte-macrophage progenitor

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

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (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
Pages (from-to)123-133
Number of pages11
JournalJournal of leukocyte biology
Volume104
Issue number1
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • eosinophil
  • granulocyte
  • hematopoiesis
  • Myb
  • neutrophil

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 A. ; de Graaf, Carolyn A. ; McKenzie, Mark D. ; Di Rago, Ladina ; Baldwin, Tracey M. ; Shortt, Jake ; Alexander, Warren S. ; Bochner, Bruce S. ; 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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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.",
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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 A.; de Graaf, Carolyn A.; McKenzie, Mark D.; Di Rago, Ladina; Baldwin, Tracey M.; Shortt, Jake; Alexander, Warren S.; Bochner, Bruce S.; 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 journalArticleResearchpeer-review

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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 A.

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 S.

AU - Ritchie, Matthew E.

AU - Hilton, Douglas J.

AU - Fairfax, Kirsten A.

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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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KW - granulocyte

KW - hematopoiesis

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KW - neutrophil

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Bolden JE, Lucas EC, Zhou G, O'Sullivan JA, de Graaf CA, McKenzie MD et al. Identification of a Siglec-F+ granulocyte-macrophage progenitor. Journal of leukocyte biology. 2018 Jul 1;104(1):123-133. https://doi.org/10.1002/JLB.1MA1217-475R