Induction of adult levels of β-globin in human erythroid cells that intrinsically express embryonic or fetal globin by transduction with KLF1 and BCL11A-XL

摘要: A major barrier to the clinical use of erythrocytes generated in vitro from pluripotent stem cells or cord blood progenitors is failure these express adult hemoglobin. The key regulators globin switching KLF1 and BCL11A are absent at a lower level than K562 erythroid differentiated induced progenitors. Transfection transduction with either BCL11A-XL had little effect on β-globin expression. In contrast, both transcription factors stimulated Similarly, increasing cell-derived cell line HiDEP-1, which has levels endogenous similar but lacks BCL11A, resulted equivalent that cells. Interestingly, this increase was coincident decrease e− ζ−, not γ-globin, implicating repression embryonic data show together required, sufficient induce blood-derived intrinsically fetal globin.