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Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor.

Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K - J. Exp. Med. (2008)

Bottom Line: Weissman. 2002.Proc.Natl.

View Article: PubMed Central - PubMed

Affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.

ABSTRACT
To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872-11877) was composed of the interleukin 5 receptor alpha chain(+) (IL-5Ralpha(+)) and IL-5Ralpha(-) fractions, and the former was the hEoP. The IL-5Ralpha(+)CD34(+)CD38(+)IL-3Ralpha(+)CD45RA(-) hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Ralpha(-) hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5Ralpha-negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.

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The comparison of lineage-affiliated gene expression between hEoPs and other myeloid progenitors. (A) RT-PCR analyses of lineage-affiliated genes. (B) Quantitative real-time PCR analyses of lineage-instructive transcription factors (Ba, blood basophils; Eo, blood eosinophils). Data were reproducible in three independent analyses using different RNA samples. Data represent means ± SEM.
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fig5: The comparison of lineage-affiliated gene expression between hEoPs and other myeloid progenitors. (A) RT-PCR analyses of lineage-affiliated genes. (B) Quantitative real-time PCR analyses of lineage-instructive transcription factors (Ba, blood basophils; Eo, blood eosinophils). Data were reproducible in three independent analyses using different RNA samples. Data represent means ± SEM.

Mentions: Consistent with their capability of functional readouts, IL-5Rα and EPX transcripts were exclusively expressed in hEoPs, whereas other eosinophil-specific genes such as Charcot-Leyden crystal protein and major basic protein were expressed at low levels in hCMPs but were up-regulated at the hEoP stage (Fig. 5 A). hMEPs and hGMPs never expressed any of these eosinophil-related molecules (Fig. 5 A).


Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor.

Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K - J. Exp. Med. (2008)

The comparison of lineage-affiliated gene expression between hEoPs and other myeloid progenitors. (A) RT-PCR analyses of lineage-affiliated genes. (B) Quantitative real-time PCR analyses of lineage-instructive transcription factors (Ba, blood basophils; Eo, blood eosinophils). Data were reproducible in three independent analyses using different RNA samples. Data represent means ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2626675&req=5

fig5: The comparison of lineage-affiliated gene expression between hEoPs and other myeloid progenitors. (A) RT-PCR analyses of lineage-affiliated genes. (B) Quantitative real-time PCR analyses of lineage-instructive transcription factors (Ba, blood basophils; Eo, blood eosinophils). Data were reproducible in three independent analyses using different RNA samples. Data represent means ± SEM.
Mentions: Consistent with their capability of functional readouts, IL-5Rα and EPX transcripts were exclusively expressed in hEoPs, whereas other eosinophil-specific genes such as Charcot-Leyden crystal protein and major basic protein were expressed at low levels in hCMPs but were up-regulated at the hEoP stage (Fig. 5 A). hMEPs and hGMPs never expressed any of these eosinophil-related molecules (Fig. 5 A).

Bottom Line: Weissman. 2002.Proc.Natl.

View Article: PubMed Central - PubMed

Affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.

ABSTRACT
To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872-11877) was composed of the interleukin 5 receptor alpha chain(+) (IL-5Ralpha(+)) and IL-5Ralpha(-) fractions, and the former was the hEoP. The IL-5Ralpha(+)CD34(+)CD38(+)IL-3Ralpha(+)CD45RA(-) hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Ralpha(-) hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5Ralpha-negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.

Show MeSH
Related in: MedlinePlus