Document Type

Journal Article

Publication Date

9-4-2014

Journal

PLoS ONE

Volume

9

Issue

9

Inclusive Pages

e106924

DOI

10.1371/journal.pone.0106924

Keywords

Anemia, Sickle Cell--genetics; Erythrocytes, Abnormal--metabolism; Fetal Hemoglobin--genetics; MicroRNAs--genetics; RNA-Binding Proteins--genetics; beta-Globins--genetics

Abstract

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes.

Comments

Reproduced with permission of PLoS ONE.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Peer Reviewed

1

Open Access

1

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