Induction of fetal hemoglobin: Lentiviral shRNA knockdown of HBS1L in β<sup>0</sup>thalassemia/HbE erythroid cells
Issued Date
2023-03-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85149764823
Pubmed ID
36888630
Journal Title
PLoS ONE
Volume
18
Issue
3 March
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.18 No.3 March (2023)
Suggested Citation
Chumchuen S., Sripichai O., Jearawiriyapaisarn N., Fucharoen S., Peerapittayamongkol C. Induction of fetal hemoglobin: Lentiviral shRNA knockdown of HBS1L in β<sup>0</sup>thalassemia/HbE erythroid cells. PLoS ONE Vol.18 No.3 March (2023). doi:10.1371/journal.pone.0281059 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/82145
Title
Induction of fetal hemoglobin: Lentiviral shRNA knockdown of HBS1L in β<sup>0</sup>thalassemia/HbE erythroid cells
Author's Affiliation
Other Contributor(s)
Abstract
Imbalanced globin chain output contributes to thalassemia pathophysiology. Hence, induction of fetal hemoglobin in β-thalassemia and other β-hemoglobinopathies are of continuing interest for therapeutic approaches. Genome-wide association studies have identified three common genetic loci: namely β-globin (HBB), an intergenic region between MYB and HBS1L, and BCL11A underlying quantitative fetal hemoglobin production. Here, we report that knockdown of HBS1L (all known variants) using shRNA in early erythroblast obtained from β0-thalassemia/HbE patients triggers an upregulation of γ-globin mRNA 1.69 folds. There is modest perturbation of red cell differentiation assessed by flow cytometry and morphology studies. The levels of α- and β-globin mRNAs are relatively unaltered. Knockdown of HBS1L also increases the percentage of fetal hemoglobin around 16.7 folds when compared to non-targeting shRNA. Targeting HBS1L is attractive because of the potent induction of fetal hemoglobin and the modest effect on cell differentiation.