α-Thalassemia-Like Globin Gene Expression by Primitive Erythrocytes Derived from Human Embryonic Stem Cells

Abstract

Under culture conditions that promote hematopoietic differentiation, human embryonic stem cells (huESC) give rise to primitive erythroid cells that closely resemble the nucleated erythrocytes of early-stage human embryos. The globin chain distribution of these cells is similar to that seen during the embryonic and fetal stages of development. Here we show that huESC-derived erythroid cells produce substantial quantities of homotetrameric hemoglobin (Hb) composed exclusively of γ-globin-containing subunits. The globin synthesis of these erythroid cells was also significantly unbalanced, with a substantial decrease of α-like globin chain synthesis in relation to that of their β-like globins, a pattern characteristically associated with α-thalassemia (α-thal). This pattern of unbalanced globin synthesis appears to be an inherent feature of human erythroid cells that synthesize predominantly embryonic-stage globins.

Keywords:

• Human embryonic stem cells (huESC)
• Embryonic stem cells
• Embryonic hemoglobins (Hbs)
• Hb γ₄ globin synthesis