The treatment of a number of diseases including hemoglobinopathies and malaria will require a fundamental understanding of human erythropoiesis. Many experimental methodologies aimed at understanding this process are inherently flawed as they involve nonhuman cells or cell lines derived from transformed cells. The study of erythropoiesis in primary erythroblasts has been handicapped by experimental pitfalls associated with the ex vivo culture of those cells. We have taken a direct approach toward the prospective study of the early transcriptional events that encompass human erythropoiesis. Using flow cytometry to analyze liquid cultured blood from normal volunteers, we have identified and temporally phenotyped the erythroid continuum of cells present in these mass cultures. This approach has led to the identification of erythroblasts that are transcriptionally committed to erythroid differentiation. Surprisingly, within that population are cells able to form giant colonies in semisolid media suggesting differentiation and proliferation are not invariably coupled in normal human hematopoiesis. The most immature hematopoietic that have committed themselves toward the transcription of erythroid-specific genes represent a pivitol cell for the study of proliferation and differentiation events associated with normal and abnormal human erythropoiesis. Our immediate future goal is the characterization of these cells by antigenic and further transcriptional phenotyping. Once the transcriptional events associated with normal erythropoiesis are defined, correlates aimed at understanding disease states involving red blood cells may be possible.
| de Vasconcellos, Jaira F; Lee, Y Terry; Byrnes, Colleen et al. (2016) HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts. PLoS One 11:e0166928 |
| Oneal, Patricia A; Gantt, Nicole M; Schwartz, Joseph D et al. (2006) Fetal hemoglobin silencing in humans. Blood 108:2081-6 |
| Miller, Jeffery Lynn (2006) Patchwork HBA1 and HBA2 genes. Haematologica 91:289A |
| Bhanu, Natarajan V; Trice, Tiffany A; Lee, Y Terry et al. (2005) A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells. Blood 105:387-93 |
| Miller, Jeffery L (2005) Signaled expression of fetal hemoglobin during development. Transfusion 45:1229-32 |
| Goh, Sung-Ho; Lee, Y Terry; Bhanu, Natarajan V et al. (2005) A newly discovered human alpha-globin gene. Blood 106:1466-72 |
| Aerbajinai, Wulin; Lee, Y Terry; Wojda, Urszula et al. (2004) Cloning and characterization of a gene expressed during terminal differentiation that encodes a novel inhibitor of growth. J Biol Chem 279:1916-21 |
| Pal, Saumen; Nemeth, Michael J; Bodine, David et al. (2004) Neurokinin-B transcription in erythroid cells: direct activation by the hematopoietic transcription factor GATA-1. J Biol Chem 279:31348-56 |
| Bhanu, Natarajan V; Trice, Tiffany A; Lee, Y Terry et al. (2004) A signaling mechanism for growth-related expression of fetal hemoglobin. Blood 103:1929-33 |
| Goh, Sung-Ho; Jackson, Kaedrea A; Terry Lee, Y et al. (2004) Identification of an alternate delta-globin mRNA in adult human erythroid cells. Genomics 84:431-4 |
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