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APOA-1 is a Novel Marker of Erythroid Cell Maturation from Hematopoietic Stem Cells in Mice and Humans

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Abstract

The mechanism that regulates the terminal maturation of hematopoietic stem cells into erythroid cells is poorly understood. Therefore, identifying genes and surface markers that are restricted to specific stages of erythroid maturation will further our understanding of erythropoiesis. To identify genes expressed at discrete stages of erythroid development, we screened for genes that contributed to the proliferation and maturation of erythropoietin (EPO)-dependent UT-7/EPO cells. After transducing erythroid cells with a human fetal liver (FL)-derived lentiviral cDNA library and culturing the cells in the absence of EPO, we identified 17 candidate genes that supported erythroid colony formation. In addition, the mouse homologues of these candidate genes were identified and their expression was examined in E12.5 erythroid populations by qRT-PCR. The expression of candidate erythroid marker was also assessed at the protein level by immunohistochemistry and ELISA. Our study demonstrated that expression of the Apoa-1 gene, an apolipoprotein family member, significantly increased as hematopoietic stem cells differentiated into mature erythroid cells in the mouse FL. The Apoa-1 protein was more abundant in mature erythroid cells than hematopoietic stem and progenitor cells in the mouse FL by ELISA. Moreover, APOA-1 gene expression was detected in mature erythroid cells from human peripheral blood. We conclude that APOA-1 is a novel marker of the terminal erythroid maturation of hematopoietic stem cells in both mice and humans.

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Acknowledgements

The authors would like to thank Chiyo Mizuochi, Yuka Horio, Tatsuya Sasaki and Michiko Ushijima at Kyushu University for excellent technical assistance. This work was supported by a grant from the Project for Realization of Regenerative Medicine from the Ministry of Education, Culture, Sports, Science and Technology and by a grant from the BASIS project from the Ministry of Education, Culture, Sports, Science and Technology. T. Inoue is supported by research fellowships from the Japan Society for the Promotion of Science for Young Scientists.

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The authors indicate no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Tomoko Inoue, Ryo Kurita, Tatsuo Oikawa, Hirotaka Kawano, Yoshie Miura, Michiyo Okada, Youko Suehiro, Atsushi Takahashi, Tomotoshi Marumoto, Hiroyuki Inoue & Kenzaburo Tani

  2. Faculty of Medical Sciences, Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Daisuke Sugiyama

  3. Faculty of Medical Sciences, Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kasem Kulkeaw

  4. Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan

    Norio Komatsu

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  1. Tomoko Inoue
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Correspondence to Kenzaburo Tani.

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Supplemental Figure 1

MTT assay of UT-7/EPO cells in the presence or the absence of EPO. We examined cell proliferation (O.D. 450 nm) at days 2, 4, 6 and 8. UT-7/EPO cells proliferated in the presence but not in the absence of EPO. (PPT 103 kb)

Supplemental Figure 2

(A) UT-7/EPO cells were cultured in the presence or absence of EPO for 3 days and then analyzed for the expression of surface markers CD71 (transferrin receptor) and GPA (glycophorin A). (B) UT-7/EPO cells were cultured in the presence or absence of EPO for 2 days and examined for fetal hemoglobin (gamma-globin) and adult hemoglobin (beta-globin). (PPT 776 kb)

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Inoue, T., Sugiyama, D., Kurita, R. et al. APOA-1 is a Novel Marker of Erythroid Cell Maturation from Hematopoietic Stem Cells in Mice and Humans. Stem Cell Rev and Rep 7, 43–52 (2011). https://doi.org/10.1007/s12015-010-9140-7

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