Recommended Conferences

Human Genetics and Genetic Disorders

Miami, USA

Tissue Engineering and Regenerative Medicine

Chicago, USA
Related Subjects
 

Erythroid-specific expression of LIN28A is sufficient for robust gamma-globin gene and protein expression in adult erythroblasts

Author(s): Lee YT, de Vasconcellos JF, Byrnes C, Kaushal M, Miller JL

Abstract

Increasing fetal hemoglobin (HbF) levels in adult humans remains an active area in hematologic research. Here we explored erythroid-specific LIN28A expression for its effect in regulating gamma-globin gene expression and HbF levels in cultured adult erythroblasts. For this purpose, lentiviral transduction vectors were produced with LIN28A expression driven by erythroid-specific gene promoter regions of the human KLF1 or SPTA1 genes. Transgene expression of LIN28A with a linked puromycin resistance marker was restricted to the erythroid lineage as demonstrated by selective survival of erythroid colonies (greater than 95% of all colonies). Erythroblast LIN28A over-expression (LIN28A-OE) did not significantly affect proliferation or inhibit differentiation. Greater than 70% suppression of total let-7 microRNA levels was confirmed in LIN28A-OE cells. Increases in gamma-globin mRNA and protein expression with HbF levels reaching 30–40% were achieved. These data suggest that erythroblast targeting of LIN28A expression is sufficient for increasing fetal hemoglobin expression in adult human erythroblasts.

Similar Articles

Forward RNAi screens in primary human hematopoietic stem/progenitor cells

Author(s): Ali N, Karlsson C, Aspling M, Hu G, Hacohen N, et al.

High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing

Author(s): Sims D, Mendes-Pereira AM, Frankum J, Burgess D, Cerone MA

HMGA2 moderately increases fetal hemoglobin expression in human adult erythroblasts

Author(s): de Vasconcellos JF, Lee YT, Byrnes C, Tumburu L, Miller JL

STAR: Ultrafast universal RNA-seq aligner

Author(s): Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C