Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and
β-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted
let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult
developmental transition. To explore the effects of LIN28B in human erythroid cell
development, lentiviral transduction was used to knockdown LIN28B expression in
erythroblasts cultured from human umbilical cord CD34+ cells. The subsequent reduction in …

HbF expression. Conversely, LIN28B overexpression in cultured adult erythroblasts reduced
the expression of let-7 and significantly increased HbF expression. Cellular maturation was
maintained including enucleation. LIN28B expression in adult erythroblasts increased the
expression of g-globin, and the HbF content of the cells rose to levels> 30% of their
hemoglobin. Expression of carbonic anhydrase I, glucosaminyl (N-acetyl) transferase 2, and
miR-96 (three additional genes marking the transition from fetal-toadult erythropoiesis) were …