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

• Published in: Stem cell reviews Vol. 7; no. 1; pp. 43 - 52
• Main Authors: Inoue, Tomoko, Sugiyama, Daisuke, Kurita, Ryo, Oikawa, Tatsuo, Kulkeaw, Kasem, Kawano, Hirotaka, Miura, Yoshie, Okada, Michiyo, Suehiro, Youko, Takahashi, Atsushi, Marumoto, Tomotoshi, Inoue, Hiroyuki, Komatsu, Norio, Tani, Kenzaburo
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.03.2011; Springer Nature B.V
• Subjects: Animals; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; Apolipoproteins; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Cell Biology; Cell Differentiation; Cell Line; Cell Proliferation; Cell Separation; Erythroid Cells - cytology; Erythroid Cells - metabolism; Erythropoietin - metabolism; Fetus - metabolism; Gene Expression Regulation, Developmental; Gene Library; Genetic Association Studies; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Humans; Lentivirus - genetics; Life Sciences; Liver - cytology; Liver - metabolism; Mice; Receptors, Erythropoietin - metabolism; Regenerative Medicine/Tissue Engineering; Signal Transduction; Stem Cells; Transduction, Genetic; Library screening; APOA-1; Erythroid cell maturation; Lentiviral cDNA library; Fetal liver erythropoiesis
• ISSN: 1550-8943; 2629-3269; 1558-6804; 2629-3277
• DOI: 10.1007/s12015-010-9140-7

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.